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A list of upcoming papers related to immunology is presented. They include "Mycobacterium tuberculosis HSP70 impairs maturation of dendritic cells from bone marrow precursors, induces IL-10 production and inhibits T-cell proliferation," "Triacylated lipoproteins derived from Mycoplasma pneumoniae activate NF-jB through TLR1 and TLR2," and " Sphingosine kinase inhibitor suppresses dendritic cell migration by regulating chemokine receptor expression and impairing p38 MAPK."

In the preceding paper a population of lymphoid cells was identified which (1) were derived from germinal centres in the appendix, (2) were localized in follicular structures elsewhere, and (3) could perform as antibody-forming cell precursors. The present paper presents evidence (1) that germinal centres in the spleen and lymph nodes perform the same function as germinal centres in the appendix, and (2) that germinal centres are dependent upon a stream of cells derived from the bone marrow. A new hypothesis is put forward regarding the origin and cellular kinetics of the B-cell system in mammals. It is proposed that germinal centres throughout the body function as an essentially antigen-dependent amplification system for the B-cell population of lymphocytes. Implications of this hypothesis are discussed. [ABSTRACT FROM AUTHOR]

As perhaps the staunchest advocates of repertoire purging as the central mechanism of immunological tolerance, we note with satisfaction a spate of recent, elegant papers which suggest an intrathymic clonal abortion model as the explanation for at least some examples of T-cell tolerance. This view agrees with the classical formulation of the Billingham-Brent-Medawar school of tolerance as a specific, central failure of immune responsiveness. Repertoire purging within the B-lymphocyte compartment remains much more controversial. There is no doubt that experimental models exist where the B cell is the reversible target of tolerance induction. The question is, in view of the ease of inducing autoantibody formation both in vivo and in vitro, just how relevant are such clonal anergy mechanisms to authentic self-tolerance? Arguments are presented that there must be two windows of tolerance susceptibility in the ontogeny of the B cell; one while it is maturing in the bone marrow, to prevent autoreactivity of high affinity to important accessible self-antigens; and a second soon after activation of pre-memory cells by exogenous antigen, to prevent fortuitous mutations towards high-affinity anti-self-reactivity establishing a forbidden clone. [ABSTRACT FROM AUTHOR]

Reagents for the identification of rabbit cell markers have been developed at a relatively slow rate. In this paper, rabbit cells are being characterized by polyclonal antibodies against a Tall antigen (RTLA), a B-cell antigen (RABELA) and an analogue of murine Ia antigen. A number of monoclonal antibodies, specific for lymphocytes and/or bone marrow and/or polymorphonuclear leucocytes, have been used for the analysis of cells with identifiable membrane antigens. Populations that have cells with two of the above antigens in the membranes were identified. To these ends, complement-mediated cell kill by antisera alone and in mixtures was employed. [ABSTRACT FROM AUTHOR]

In this paper we describe production of alloantisera specific for determinants encoded by I-J gene loci expressed on macrophages. B10.A(3R) (l-Jb) mice were hyperimmunized with pure populations of macrophages grown in vitro from bone marrow stem cells of congenic B10.A(5R) mice. The antisera contained predominantly IgM antibody that was non-adherent to protein-A-Sepharose with a minor component of IgGI, and IgG2a antibodies that were adherent to protein.A-Sepharose. The protein- A non-adherent antibody completely blocked the in vitro generation of humoral immune responses to sheep erythrocytes by spleen cell from B10.A(5R) mice and from inbred strains that share the I-Jk haplotypes, but did not alter the responses of spleen cells of the I-Jb haplotype. In the presence of complement. both protein-A adherent and protein-A non-adherent antibodies eliminated the capacity of B10.A(5R) spleen cells to generate humoral and proliferative responses, but the functional activity of B10.A(3R) cells was unaffected. These data indicate the I-Jk specificity of the antisera. The capacity of the anti-macrophage antibody to block humoral immune induction was removed by absorption with bone marrow-derived macrophages from B10.A(5R) mice, but not from B10.A(3R) mice. Further, the B10.A(5R) macrophages completely restored the humoral responses of antibody- and complement-treated B10.A(5R) spleen cells, but B10.A(3R) macrophages showed only partial restoration that was consistent with a factor-mediated allogeneic effect. These data demonstrate the specificity of our anti-I-J sera for macrophages and indicate that bone marrow-derived macrophages express surface I-J encoded molecules. [ABSTRACT FROM AUTHOR]

In the present paper it is shown that the non-species specific determinant of the antigenic thymus-brain system previously detected in murine and human brain also exists in human thymus. However, in contrast to the situation in mice and rats this antigenic structure is not expressed on suspended thymic lymphocytes, but is associated with thymic tissue largely depleted of thymic lymphocytes. Moreover, this determinant is also detectable in human lymph nodes. Besides the non-species-specific antigenic determinant human thymus and brain also share a species-specific determinant. In contrast to the non species specific determinant this structure is also displayed by suspended thymic lymphocytes, certain peripheral blood lymphocytes and bone marrow cells. The non-species-specific determinant detected in human thymus is borne by a structure, which physico-chemically resembles the thymus-brain antigen isolated from murine brain and thymus as well as from human brain. Although the structure bearing the species specific antigenic determinant has a similar apparent molecular weight both antigens could be separated by ion exchange chromatography indicating their molecular diversity. [ABSTRACT FROM AUTHOR]

Mouse bone marrow is capable of a distinct plaque-forming cell (PFC) response after i.v. immunization with the thymus-independent antigen E. coli lipopolysaccharide (LPS). Both during the primary and secondary response to i.v. administered LPS the spleen contained the majority of PFC until about 5 days after immunization. In the course of the reaction the number of PFC in the bone marrow rose to a level which surpassed the level in the spleen. This paper deals with the regulating influence of the spleen on the primary and secondary anti-LPS PFC response in the bone marrow. Splenectomy prior to the first injection of 5 μg LPS i.v. initially did not affect the bone marrow PFC response. However, at the 7th day after immunization the PFC response in the bone marrow fell to only 10 per cent of the bone marrow PFC activity in sham-splenectomized mice. In contrast to the primary response no regulating influence of the spleen on the bone marrow PFC activity could be demonstrated during the secondary response. The influence of splenectomy on the appearance of B-memory cells in the bone marrow depended on the priming dose. The appearance of LPS-specific B-memory cells in the bone marrow was not affected by splenectomy at priming doses of LPS as high as 1 and 0.1 μg. On the other hand splenectomy before 0.01 μg LPS i.v. reduced, and splenectomy prior to 0.001 μg LPS i.v. completely prevented the appearance of B-memory cells in the bone marrow. [ABSTRACT FROM AUTHOR]

Conventional dendritic cells (cDCs) arise from committed precursor dendritic cells (pre‐DCs) in the bone marrow that continuously seed the periphery. Pre‐DCs and other upstream progenitors proliferate and mature in response to Fms‐related receptor tyrosine kinase 3 ligand, which is considered the key cytokine for cDC development. However, other cytokines such as stem cell factor and colony‐stimulating factor 1 (CSF1) were also shown to induce pre‐DC maturation into DC‐like cells. Yet, it is still only incompletely understood which cells contribute to cDC development once pre‐DCs arrive in peripheral tissues. Here, we analysed the impact of lymph node (LN) fibroblastic stromal cells (FSCs) on the maturation of pre‐DCs into cDC‐like cells. We could demonstrate that ex vivo isolated LN FSCs co‐cultured with pre‐DCs induce precursor maturation into DC‐like cells, which were capable of efficiently promoting the proliferation of naïve CD4+ T cells. Interestingly, FSCs isolated from distinct LNs induced DC‐like cells with highly comparable transcriptomes, characterized by the expression of signature genes of both ex vivo isolated DCs and macrophages. Finally, by performing supplementation and receptor blocking studies, we could demonstrate that CSF1 is a driving factor for LN FSC‐mediated pre‐DC maturation into DC‐like cells. In summary, we could identify CSF1 as a stromal cell‐derived factor that has the potential to support the maturation of pre‐DCs into cDC‐like cells within secondary lymphoid organs. [ABSTRACT FROM AUTHOR]

Monocytes play a crucial role in maintaining homeostasis and mediating a successful innate immune response. They also act as central players in diverse pathological conditions, thus making them an attractive therapeutic target. Within the bone marrow, monocytes arise from a committed precursor termed Common Monocyte Progenitor (cMoP). However, molecular mechanisms that regulate the differentiation of cMoP to various monocytic subsets remain unclear. Herein, we purified murine myeloid precursors for deep poly‐A‐enriched RNA sequencing to understand the role of alternative splicing in the development and differentiation of monocytes under homeostasis. Our analyses revealed intron retention to be the major alternative splicing mechanism involved in the monocyte differentiation cascade, especially in the differentiation of Ly6Chi monocytes to Ly6Clo monocytes. Furthermore, we found that the intron retention of key genes involved in the differentiation of murine Ly6Chi to Ly6Clo monocytes was also conserved in humans. Our data highlight the unique role of intron retention in the regulation of the monocytic differentiation pathway. [ABSTRACT FROM AUTHOR]

B‐cell development undergoes a series of steps from the bone marrow to the secondary lymphoid organs. A defect in B‐cell development can lead to immunodeficiency or malignant disorders, such as leukaemia or lymphoma. Long non‐coding RNAs have been reported to act as important regulators of many pathological processes. However, very little is known regarding the role of lncRNAs during B‐cell development and the regulation of their expression. In this study, we explored the expression and role of lncRNA Gme00492 in B‐cell development. We observed that lnc00492 was highly expressed in B‐cell development and primarily expressed in the nucleus. Lnc00492‐deficient mice had fewer marginal zone B cells in the spleen, likely due to a developmental block. Importantly, lnc00492 interacts with CTBP1 and targets it for ubiquitination and degradation during B‐cell development, whereas the transcriptional corepressor factor CTBP1 plays a critical role in Notch2 signalling. Thus, we identified a novel regulatory axis between lnc00492 and CTBP1 in B cells, suggesting that lnc00492 is essential for marginal zone B‐cell development. [ABSTRACT FROM AUTHOR]

With a long history of promoting pathological inflammation, eosinophils are now emerging as important regulatory cells. Yet, findings from controlled laboratory experiments so far lack translation to animals, including humans, in their natural environment. In order to appreciate the breadth of eosinophil phenotype under non‐laboratory, uncontrolled conditions, we exploit a free‐living population of the model organism Mus musculus domesticus. Eosinophils were present at significantly higher proportions in the spleen and bone marrow of wild mice compared with laboratory mice. Strikingly, the majority of eosinophils of wild mice exhibited a unique Ly6Ghi phenotype seldom described in laboratory literature. Ly6G expression correlated with activation status in spleen and bone marrow, but not peritoneal exudate cells, and is therefore likely not an activation marker per se. Intermediate Ly6G expression was transiently induced in a small proportion of eosinophils from C57BL/6 laboratory mice during acute infection with the whipworm Trichuris muris, but not during low‐dose chronic infection, which better represents parasite exposure in the wild. We conclude that the natural state of the eosinophil is not adequately reflected in the standard laboratory mouse, which compromises our attempts to dissect their functional relevance. Our findings emphasize the importance of studying the immune system in its natural context – alongside more mechanistic laboratory experiments – in order to capture the entirety of immune phenotypes and functions. [ABSTRACT FROM AUTHOR]

The bone marrow of young adult nude mice was investigated as a site of antibody formation after intravenous immunization with the thymus-independent antigen Escherichia coli lipopolysaccharide (LPS). Mice heterozygous for the nu-gene were found to be capable of a plaque-forming cell (PFC) response in both spleen and bone marrow after primary and secondary immunization with LPS. Primary immunization of nude mice with LPS induced a normal PFC response in the spleen, but did not evoke the appearance of PFC in the bone marrow. During the secondary response the nude mice did show PFC activity in the bone marrow, but at a much lower level than their heterozygous littermates. At all time points after secondary immunization the number of splenic PFC was higher in nude mice than in the control mice. Determination by immunofluorescence of cells containing cytoplasmic immunoglobulin (C-Ig cells) in the bone marrow of young adult nonimmune nude and heterozygous mice, revealed a three times higher number of C-IgM cells in the bone marrow of the heterozygous thymus-bearing mice. On the other hand, the number of splenic C-IgM cells was higher in the nude mice than in their heterozygous littermates. These results suggest that the presence of the thymus facilitates the appearance of mature antibody-forming cells in the bone marrow of young adult mice, irrespective of whether the generation of these cells is initiated by so called thymus-dependent or thymus-independent antigens. [ABSTRACT FROM AUTHOR]

The enhancement effect of some antigens on in vitro colony formation by normal mouse bone marrow cells is mediated through a normal serum αmacroglobulin (αM) which is present in newborn animals and shows no immunological specificity. The proportion of antigen and αM affects colony enhancement, and it has also been shown that specific antibody successfully competes with αM for the antigen. It seems likely that antigen-αM complex acts directly on the colony forming cell, rather than indirectly through release of colony stimulating factor. The possible relevance of this phenomenon to immune induction and, to the effect of antigens in promoting irradiation survival is discussed. [ABSTRACT FROM AUTHOR]

Summary: Tbet‐deficient mice have reduced natural killer (NK) cells in blood and spleen, but increased NK cells in bone marrow and lymph nodes, a phenotype that is thought to be the result of defective migration. Here, we revisit the role of Tbet in NK cell bone marrow egress. We definitively show that the accumulation of NK cells in the bone marrow of Tbet‐deficient Tbx21−/− animals occurs because of a migration defect and identify a module of genes, co‐ordinated by Tbet, which affects the localization of NK cells in the bone marrow. Cxcr6 is approximately 125‐fold underexpressed in Tbx21−/−, compared with wild‐type, immature NK cells. Immature NK cells accumulate in the bone marrow of CXCR6‐deficient mice, and CXCR6‐deficient progenitors are less able to reconstitute the peripheral NK cell compartment than their wild‐type counterparts. However, the CXCR6 phenotype is largely confined to immature NK cells, whereas the Tbet phenotype is present in both immature and mature NK cells, suggesting that genes identified as being more differentially expressed in mature NK cells, such as S1pr5, Cx3cr1, Sell and Cd69, may be the major drivers of the phenotype. [ABSTRACT FROM AUTHOR]

Summary: T helper type 2 (Th2) cells, type 2 innate lymphoid cells (ILC2s) and eosinophil progenitors have previously been described to produce interleukin‐5 (IL‐5) in the airways upon allergen provocation or by direct administration of IL‐33. Eosinophilic airway inflammation is known to be associated with IL‐5‐dependent eosinophil development in the bone marrow, however, the source of IL‐5 remains unclear. T helper cells, ILC2s and CD34+ progenitors have been proposed to be involved in this process, therefore, we investigated whether these cells are taking part in eosinophilopoiesis by producing IL‐5 locally in the bone marrow in IL‐33‐driven inflammation. Airway exposure with IL‐33 led to eosinophil infiltration in airways and elevated eotaxin‐2/CCL24. Importantly, IL‐5 production as well as expression of the IL‐33 receptor increased in ILC2s in the bone marrow under this treatment. A small but significant induction of IL‐5 was also found in CD34+ progenitors but not in T helper cells. Similar results were obtained by in vitro stimulation with IL‐33 where ILC2s rapidly produced large amounts of IL‐5, which coincided with the induction of eosinophil hematopoiesis. IL‐33‐mediated eosinophil production was indeed dependent on IL‐5 as both airway and bone marrow eosinophils decreased in mice treated with anti‐IL‐5 in combination with IL‐33. Interestingly, the responsiveness of ILC2s to IL‐33 as well as IL‐33‐induced eotaxin‐2/CCL24 were independent of the levels of IL‐5. In summary, we demonstrate for the first time that IL‐33 acts directly on bone marrow ILC2s, making them an early source of IL‐5 and part of a process that is central in IL‐33‐driven eosinophilia. [ABSTRACT FROM AUTHOR]

CD38 is a 45 000 molecular weight transmembrane protein that is expressed in immature and mature lymphocytes. However, the expression and function of CD38 during B-cell differentiation in mice is poorly understood. Here, we report that CD38 is expressed from the earliest stages of B-cell development. Pre-pro- B, pro- B, pre- B and immature B cells from murine bone marrow all stained positive for CD38. Interestingly, CD38 expression increases with B-cell maturation. To assess the role of CD38 during B-cell maturation, CD38-deficient mice were analysed. CD38−/− mice showed a significant increase in both the frequency of B-lineage cells and the absolute numbers of pre-pro- B cells in bone marrow; however, no other differences were observed at later stages. CD38 cross-linking in Ba/ F3 cells promoted apoptosis and marked extracellular signal-regulated kinase ( ERK) phosphorylation, and these effects were reduced by treatment with the mitogen-activated protein kinase/ ERK kinase inhibitor PD98059, and similar effects were observed in B-cell precursors from bone marrow. These data demonstrate that B-cell precursors in mouse bone marrow express functional CD38 and implicate the early ligation of CD38 in the ERK-associated regulation of the B-lineage differentiation pathway. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus ( EBV) infection may initiate production of autoantibodies and development of cancer and autoimmune diseases. Here we outline phenotypic and functional changes in B cells of patients with rheumatoid arthritis ( RA) related to EBV infection. The B-cell phenotype was analysed in blood and bone marrow ( BM) of RA patients who had EBV transcripts in BM ( EBV+, n = 13) and in EBV− ( n = 22) patients with RA. The functional effect of EBV was studied in the sorted CD25+ and CD25− peripheral B cells of RA patients ( n = 18) and healthy controls ( n = 9). Rituximab treatment results in enrichment of CD25+ B cells in peripheral blood ( PB) of EBV+ RA patients. The CD25+ B-cell subset displayed a more mature phenotype accumulating IgG-expressing cells. It was also enriched with CD27+ and CD95+ cells in PB and BM. EBV stimulation of the sorted CD25+ B cells in vitro induced a polyclonal IgG and IgM secretion in RA patients, while CD25+ B cells of healthy subjects did not respond to EBV stimulation. CD25+ B cells were enriched in PB and synovial fluid of RA patients. EBV infection affects the B-cell phenotype in RA patients by increasing the CD25+ subset and by inducing their immunoglobulin production. These findings clearly link CD25+ B cells to the EBV-dependent sequence of reactions in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]

In mice, the plasma cell (PC) niche in the bone marrow is close to the haematopoietic stem cell (HSC) niche. We investigated whether PCs can be mobilized into the peripheral blood (PB) in healthy donors receiving granulocyte colony-stimulating factor (G-CSF) for the induction of HSC mobilization into the PB. G-CSF increased the count of circulating PCs 6-fold, that of circulating B lymphocytes 4-fold and that of circulating HSCs 44-fold. Mobilized circulating PCs comprised CD138 (62·2%) and CD138 (37·8%) PCs, the latter being more mature based on increased CD27, CD38 and cytoplasmic immunoglobulin expression. Mobilized PCs had a phenotype close to that of steady-state PB PCs or in vitro generated PCs, but they expressed L-selectin only weakly. Finally, a median value of 0·4 × 10/kg donor PCs - one-thirtieth of the overall PC count in a healthy adult - was grafted into patients, which could contribute to immune memory recovery. [ABSTRACT FROM AUTHOR]

Many effects of environmental toxic agents contribute to the deregulation of immune system homeostasis. Here we demonstrate that the effect of airborne suspended matter (ASM) on the generation of mouse T cells is reversible. This reversal can be achieved by an active process that returns the T cells to homeostasis and does not result from the simple effect of ASM deprivation. An accelerated development of thymocytes and increased influx of T-cell progenitors to the thymus in mice exposed to environmental xenobiotics has been postulated. This hypothesis has been confirmed by parallel increases in the percentages of single-positive and triple-negative thymocytes. Enhanced expression of thymocyte surface markers related to positive selection has also been observed. The pathway of T-cell progenitor development is favoured in the bone marrow of mice exposed to ASM. [ABSTRACT FROM AUTHOR]

Rat mast cells with the properties of mucosal mast cells (MMC) proliferate in cultures of haemopoietic tissue in the presence of conditioned medium (CM) from antigen- or mitogen-activated T lymphocytes. The present study shows that recombinant rat interleukin-3 (rIL-3) both stimulated the development of MMC from bone marrow (BM) precursors and maintained the proliferation of rat MMC lines in an identical manner to that of CM. The content per cell of the MMC granule- specific proteinase RMCPII was similar in both IL-3- and CM-stimulated cultures. Passage of CM through DEAE-cellulose separated two active peaks that stimulated autologous MMC proliferation. The biochemical properties of peak 1 were similar to those of murine IL-3 and stimulated multi-potential stem cell development in soft agar cultures of SM cells from rats treated with 5- fluorouracil (which enriches for haemopoietic stem cells). RIL-3 was also active in this assay whereas peak 2 was not, demonstrating that peak I contained IL-3 activity. The presence of MMC in the majority of multi-potential colonies in the soft agar cultures confirmed the early stem cell origin of the MMC lineage. The cultured SM-derived mast cells in the rat are analogues of the MMC subset that is most readily observed proliferating in the gastrointestinal tract in response to helminth parasite infection. The demonstration that IL-3 is responsible for the development and proliferation of MMC should lead to a better understanding of the functional roles of these cells. [ABSTRACT FROM AUTHOR]

Ovine mast cells generated in vitro are morphologically and biochemically similar to mast cells localized to the gastrointestinal tract in vivo. Bone marrow (BM)-derived haemopoietic precursor cells were cultured in the presence of conditioned medium (CM) prepared from in vitro-activated lymphocytes from nematode-infected sheep. Mast cells developed rapidly after 2 weeks of culture and could persist for 2-3 months. The presence of sheep mast cell proteinase (SMCP) in the cultured cells correlated with the number of morphologically recognizable mast cells by Leishman-Giemsa staining and is definitive as, in vivo, this enzyme is unique to mast cells. The content of SMCP per cell increased as the cultures developed. In vivo, increased serum concentrations of SMCP are associated with mast cell function at the site of nematode infection. The availability of the cultured cells should now facilitate mast cell biochemical and functional studies. [ABSTRACT FROM AUTHOR]

The site and mechanism of recruitment of short-lived new B cells from the bone marrow into the longer-lived recirculating B-cell pool were studied by using kappa-allotype-distinct congenic rats to construct bone marrow chimeras. Chimeras were immunized with antigen in the form of an antigen- antibody complex that is largely restricted to lymphoid follicles, rapidly localizing to follicular dendritic cells (FDC). This form of antigen, although a potent stimulator of memory B cells, was shown to be a very poor inducer of virgin B-cell responses. This was not due solely to differences in receptor affinity, as complexes in which the hapten epitopes were unmasked also evoked little virgin B-cell response. The inability of virgin B cells to be activated by FDC-bound antigen seems to relate to the fact that they are not pan of the recirculating pool and do not migrate through lymphoid follicles; restriction of antigen to a draining lymph node also precluded virgin B-cell activation. The evidence presented suggests that activation of virgin B cells at extrafollicular sites in the spleen (red pulp, marginal zone, outer periarteriolar lymphocytic sheath) is required for both their incorporation into immune responses and into the recirculating pool. These experiments also show that established immune responses are maintained by clones activated soon after immunization and not by continued incorporation of new clones. [ABSTRACT FROM AUTHOR]

Homogenous populations of human mast cells were differentiated and grown by culturing bone marrow cells in the presence of conditioned medium derived from lectin-stimulated human peripheral blood mononuclear cells. The cells obtained were similar in ultrastructure, proteoglycan type and lipid products generated upon calcium ionophore A23187, and immunological activation to the murine E-mast cells (E-MC) differentiated in culture containing IL-3. Fluorescense analysis revealed that the human E-MC expressed IgE-Fc receptors which retained bound IgE through several washes. These cells did not express cell-surface lymphoid determinants (T11, T4, T8 and B4) and myeloid determinants ‘My’. However, 40% of these cells expressed monocytic surface determinants, such as M-1. The amount of histamine that was found per 106 cells was 525 ng±106 ng (mean ±SE, n=4). These cultured mast cells possessed granular chondroitin sulphate E proteoglycan of about 180,000 MW. Following activation with either calcium ionophore A23187 or anti-hIgE challenge, these mast cells released their preformed mediators and generated mainly leukotriene C4 leukotriene B4, and platelet-activating factor. In conclusion, according to all of these criteria, these human cultured mast cells show many similarities to the murine cultured E-mast cells, and therefore could be considered as the culture analogue of the human intestinal E-mast cells identified recently. [ABSTRACT FROM AUTHOR]

A simple and highly reproducible bone marrow culture system for the generation of cytolytically active NK cells from immature precursors in the bone marrow is described. The NK cells can be generated with various sources of IL-2, including Con A-conditioned medium, supernatants from IL- 2-producing cell lines and recombinant IL-2. Neither IL-1, IL-3 nor α/β interferon induced significant cytotoxicity in bone marrow cells. Identification of the cytotoxic cells as NK cells was based on their phenotypic characteristics (aGMI+, Thy 1±, Ly 1-2-. Ia-, RlL-2±, H2+), as well as their spectrum of target specificity. The deliberate addition of peripheral blood mononuclear cells as a source of mature NK cells and elimination of cells expressing markers specific for mature NK cells indicated that the generated NK cells were descendants of precursors of NK cells harboured in the bone marrow and not derived from mature NK cells contaminating the bone marrow preparations. Thus, it was shown that not only functionally active NK cells but also their precursors are highly dependent on IL-2 for differentiation and growth. This culture system should be helpful in studying the origin of NK cells in relation to other cell lineages as well as the regulation of the maturation of NK cells from their precursors. [ABSTRACT FROM AUTHOR]

We have previously shown that lymphocytes from Nippostrongylus brasiliensis infected rats, when stimulated with antigen or concanavalin A (Con A) release factors which are comparable with murine 11-3. On addition of these factors to rat bone marrow cultures, mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) proliferate and mature. Here, we use this system, along with monoclonal antibodies against rat T cells and the fluorescence-activated cell sorter (FACS), to isolate the subset of T cells responsible for the production of this MMC growth factor. Lymphocytes from N. brasiliensis infected rats were separated on the FACs into populations with and without the antigens defined by OX19, W3/25 and OX8 monoclonal antibodies; these antibodies label all T cells, T-helper cells and T-cytotoxic/suppressor cells, respectively. The resultant subsets were cultured in vitro with Con A. The supernatants were tested for the ability to induce MMC growth and differentiation in liquid cultures of normal rat bone marrow. The phenotype of the T cells producing this factor was established as being OX19+, W3/25+ and OX8-. [ABSTRACT FROM AUTHOR]

Spleen cells from mice undergoing a parasite-induced eosinophilia were fused with an azaguanine-resistant subline of the thymoma 8W5147. A stable T hybrid (NIMP-TH1) was isolated and selected by recloning repeatedly by limiting dilution. The hybrid nature of NIMP-TH1 was confirmed by its expression of both parental alleles of Thy-1 and by chromosome analysis (modal chromosome number 102). On stimulation with phorbol myristate acetate, this hybrid releases a soluble activity which acts as a stimulator of eosinophil differentiation in vitro. Addition of hybrid conditioned medium to bone marrow cultures results in a selective stimulation of eosinophil production with no detectable increase in neutrophil or macrophage differentiation. The lymphokines interleukin-2 (IL-2) and interferon (IFN) are undetectable in NIMP-TH1 conditioned media. Although at high concentrations NIMP-TH I supernatants are able to support very low levels of DNA synthesis in an IL-3-dependent cell line, and IL-3 appears to support low levels of eosinophil differentiation, dose-response curves show that the factor produced by NIMP-TH1 can be clearly segregated from IL-3 by its marked specificity for cells belonging to the eosinophil lineage. The factor present in these supernatants has been provisionally termed eosinophil differentiation factor (EDF). [ABSTRACT FROM AUTHOR]

Human T-lymphocyte cell precursors are driven to proliferate in vitro and to form T-cell colonies during incubation with a PHA-stimulated lymphocyte supernatant (P-SUP). By using cell affinity chromatography, we selected different populations of putative T-lymphocyte precursors in the blood and bone marrow. T-colony forming cells (T-CFC) were found in each of these different populations of cells with phenotypically immature cell surface markers: OKT11- cells or OKT4-/OKT8- cells in the blood and bone marrow, and OKT10+ or RFB-l+ cells in the bone marrow. Pretreatment with OKT3, together with a monoclonal anti-DR antibody and complement, did not abrogate the T-colony forming capacity. The OKT4-/OKT8- precursors were more radiosensitive (Do= 105 rads) than OKT4+, OKT8+ cells (Do =360 rads) in their T-colony forming capacity. These results suggest that T-CFC could be induced to grow in agar from cells populations representing early steps of the T-cell lineage. [ABSTRACT FROM AUTHOR]

Infection of nude mice with Mesocestoides cord results in spleen enlargement, with a decrease in percentage positive, but overall increase in Thy-1 positive cells. A low frequency of both parasite antigen-specific and alloantigen- reactive T-cell clones were isolated from the spleen, mesenteric lymph nodes, peritoneal exudate and Peyer's patches. The T-cell clones from spleen were found to express the antigens Thy- 1, Lyt-1 and Lyt-2; furthermore, after stimulation with antigen in the absence of exogenous T cell growth factor (IL-2), they produced normal levels of haemopoietic growth factor (IL-3), bone marrow proliferation activity and eosinophil differentiation activity. A higher proportion produced IL-2 compared to clones from normal mice. The isolation of antigen-specific 1-cell clones showing normal T-cell characteristics from young nude mice adds weight to suggestions that exposure to antigen results in significant extra-thymic T-cell maturation. [ABSTRACT FROM AUTHOR]

Reciprocal radiation bone marrow chimaeras were made between H-2-compatible strains of mice innately resistant or susceptible to visceral leishmaniasis. In initial experiments, susceptibility but not resistance to Leishmania donovani could be transferred with donor bone marrow into irradiated recipients. In subsequent experiments it was possible to transfer both resistance and susceptibility. This was achieved either by selecting more radiosensitive mouse strains as susceptible recipients, or alternatively by increasing the irradiation dose for the susceptible recipients used in the initial experiments. Using the higher irradiation dose, successful transfer of resistance and susceptibility between congenic mice carrying the Lshr and Lsh3 alleles on the more radioresistant B10 genetic background provided firm evidence that the results obtained in this study were specifically related to expression of the Lsh gene. We conclude that Lsh gene-controlled resistance and susceptibility to L. donovani is determined by bone marrow-derived cells. The cell type(s) involved is likely to be of the macrophage lineage. [ABSTRACT FROM AUTHOR]

Serum from microfilaraemic patients have been shown to be unable to promote the antibody-dependent, cell-mediated adherence reaction to infective larvae of Brugia malayi in vitro. In this study, it was found that peripheral leucocytes from microfilaraemic patients were also incapable of promoting the adherence reaction even when incubated with serum of tropical pulmonary eosinophilia (TPE) patients. The TPE sera would normally promote the most intense adherence reaction. It was further shown that preincubation of normal human peripheral leucocytes with sera of microfilaraemic patients would similarly render them incapable of adherence. Such preliminary studies suggest that blocking factors may be present in microfilaraemic patients. [ABSTRACT FROM AUTHOR]

The distribution of background Ig-secreting cells, measured as cells containing cytoplasmic immunoglobulin (C-Ig cells), over spleen, bone marrow, lymph nodes and Peyer's patches was studied in congenitally athymic (nude) mice and heterozygous euthymic mice as a function of age and immune status (germ-free (GF) vs specific pathogen-free (SPF)). In young athymic as well as in young euthymic mice, the spleen was found to contain the great part of all C-Ig cells, irrespective of whether the mice were GF or SPF. The number of C-Ig cells in the spleen was found to be rather constant over the life span, while the number of C-Ig cells in the bone marrow of all groups of mice greatly increased with age. This indicates that the relative shift of C-Ig cells to the bone marrow is neither dependent on the presence of the thymus, nor on the microbiological status of the mice. However, at young and intermediate age the microbiological status of the mice did affect the total number of C-Ig cells per mouse. This was mainly due to the effect upon the bone marrow, mesenteric lymph nodes and Peyer's patches. At these ages the background Ig synthesis in these organs appeared to be mainly dependent on external antigenic stimulation, in contrast to the spleen, where the Ig synthesis appeared to be mainly due to endogenous stimulation. The Ig (sub)class distribution of the C-Ig cells was different for all different organs tested. Hardly or no difference in percentage distribution was found between the GF nude and GF heterozygous mice. Most C-Ig cells in spleen, bone marrow and lymph nodes of the GF mice were of the IgM isotype. C-IgG and C-IgA cells occurred in substantial percentages only in bone marrow and lymph nodes. In the lymph nodes of GF nude mice a remarkably high percentage of C-IgA cells was found. [ABSTRACT FROM AUTHOR]

Allogeneic irradiation bone marrow chimeras made according to a new protocol with unmanipulated bone marrow are long lived, healthy and stable full chimeras (H-2d→H-2b. Their immunocompetence is split. Alloreactivity measured by skin graft rejection and mixed lymphocyte culture is within normal range. In contrast, major histocompatibility complex (MHC)-restricted T-cell-dependent primary responses against sheep red blood cells (SRBC) or viruses are clearly deficient. The quantitative difference in immunocompetence is at least of the order of ten- to thirty-fold. The implications of the findings for lymphohaemopoietic reconstitution of immunodeficient patients are briefly discussed. [ABSTRACT FROM AUTHOR]

During the secondary response of mice to T-dependent antigens, antibody-producing plaque-forming cells (PFC) appear not only in peripheral lymphoid organs, but also in the bone marrow. This bone marrow antibody formation is feeble after primary immunization. The capacity of bone marrow antibody formation is dependent on the presence of antigen-specific memory cells at the moment of secondary immunization. We investigated whether hapten-primed B memory, carrier-primed T memory or both B-memory and T-memory cells are required for the adoptive PFC response in the bone marrow to T-dependent hapten-carrier conjugates. Adoptive antibody formation in the bone marrow was found after transfer of hapten-primed spleen cells, but not after transfer of carrier-primed spleen cells or virgin spleen cells. Thus, B-memory cells are obligatory for adoptive antibody formation in the bone marrow, in contrast to T-memory cells. However, T-memory cells did facilitate the bone marrow PFC response mediated by the infused B-memory cells. [ABSTRACT FROM AUTHOR]

Hybridoma antibodies were produced by fusing spleen cells from mice immunized with rat alveolar macrophages (AM) with P3 × 63Ag8/653 myeloma cells. Some of the hybridomas were processed to achieve monoclonality. Reactivity was tested in an indirect membrane immunofluorescence assay. One of the monoclonal antibodies, called VEP6 antibody, reacted with rat AM but not with peritoneal or splenic macrophages and not with peripheral blood monocytes of this species. It was also unreactive with cells from thymus, bone marrow, non-adherent spleen cells, granulocytes and erythrocytes, but it reacted with thrombocytes. Corynebacterium parvum activated AM were slightly less reactive than 'resident' AM, as determined in a fluorescence activated cell sorter. The VEP6 antigen was studied in polyacrylamide gel electrophoresis after immunoprecipitation from 125I -surface-labelled-macrophage NP40-lysates. Four specific radioactive bands were seen in the precipitates corresponding to molecular weights of 31, 33, 35 and 37,000. A slurred band was seen in this molecular weight range when immunoprecipitates of surface labelled thrombocytes were analysed. This study confirms the heterogeneity of macrophages by showing that certain antigens may be expressed only on a subpopulation of macrophages. [ABSTRACT FROM AUTHOR]

The routine bone marrow population mainly responsible for the unique competing activity of this lymphoid organ in the competition radio- immunoassay (cRIA) for AKR murine leukaemia viruses gp71 has been partially purified and characterized. That population could be distinguished by the following properties; (i) gp71+ cells (cell population expressing the AKR MuLV gp71 antigen) are mainly medium density cells, according to their distribution in the layers of a discontinuous bovine serum albumin (BSA) gradient; (ii) The gp71 positive cells are not mature lymphocytes; (iii) This cell population is found both in the FcR+ and FcR- compartments and is not included in the complement (C×) receptor-positive population; and finally, (iv) the gp71+ cells are phagocytic cells and an adherent ceil population according to its capacity to adhere to plastic surfaces, nylon wool and Sephadex G-10. [ABSTRACT FROM AUTHOR]

The possibility of a homeostatic control on the production of B cells was studied in CBA mice following whole body irradiation (750 fads). Bone marrow cells from femurs shielded from irradiation were taken at 24 h and the number of surface immunoglobulin positive cells assessed with a fluorescence-activated cell sorter after 24 h in vitro. The cells from the irradiated shielded mice showed greater absolute number of ‘bright’ B cells with a high density of surface immunoglobulin (mean increase 60%–100%) than cells from control unirradiated mice. These bright B cells did not incorporate (3H) thymidine in vitro and treatment with hydroxyurea (an inhibitor of DNA synthesis) did not prevent their increase. It was concluded that the increased number of bright B cells in vitro arose from augmented maturation or differentiation and not from a proliferative process. [ABSTRACT FROM AUTHOR]

Passage of spleen or bone marrow cells from non-immunized donors through a DNP-Ova coated Degalan bead immunoadsorbent column resulted in a specific depletion of the ability of the cell population to restore the anti-DNP antibody response to DNP-BGG by lethally irradiated mice. There was a preferential depletion of precursors of high affinity antibody-secreting cells which is consistent with the view that these cells bear high affinity antigen receptors The cell population passed through the immunoadsorbent column was also preferentially depleted of the capacity to produce high affinity direct anti-DNP PFC in comparison with high affinity indirect anti-DNP PFC These findings suggest, but do not prove, that different subpopulations of antigen. binding cells are precursors for direct and indirect PFC. [ABSTRACT FROM AUTHOR]

The ability of small and large T precursor cell pools to differentiate into mature functional T lymphocytes on thymus feeder cell layers or in the presence of a supernatant prepared from such feeder layers was compared. Evidence was obtained showing that the small cell pool differentiated as effectively in the presence of soluble factors prepared from the thymus cultures as in the presence of the thymus cells themselves. In contrast, large stem cells apparently needed cellular contact with the thymus feeder cultures in order to promote differentiation, though a time point could be found at which further differentiation from this precursor pool would also occur in the presence of the thymus culture supernatant only. These data concurred with evidence from in vivo experiments for two pools of T-cell precursors which differentiated in thymectomized or thymus-intact recipients respectively. [ABSTRACT FROM AUTHOR]

CBA/J mice receiving multiple injections of sodium caseinate (CAS) or bovine serum albumin (BSA) were assayed for marrow dependent functions by measuring their ability (i) to reject bone marrow allografts and (ii) to resist Friend virus (FV)induced suppression of lymphocyte mitogenesis. Mice that developed amyloidosis following 25-30 injections completely lost the ability to reject allogeneic marrow cells, whereas nonamyloid BSA-treated mice had enhanced rejection of marrow allografts. There was increased resistance to the suppressive effects of FV in spleen cells from 'preamyloid' mice receiving CAS injections and nonamyloid mice receiving 10-40 BSA injections. Amyloid mice appeared to be as susceptible to the effects of FV-induced suppression as control (untreated) animals. These data indicate that alterations in marrow dependent function may be related to the pathogenesis of amyloid disease. [ABSTRACT FROM AUTHOR]

Antiserum specific for hamster thymus-derived lymphocytes, prepared by immunization of rabbits with brain tissue from MHA/ssLAK hamsters, was, in the presence of guinea-pig complement, cytotoxic to hamster thymocytes > lymph node cells >spleen cells, while virtually unreactive against bone marrow cells. This antiserum markedly inhibited spleen cell response to the T cell mitogen, Concanavalin A, while the response to the B and T cell mitogen, pokeweed, was much less inhibited. These in vitro effects of the anti-hamster T cell serum were confirmed by utilizing lymphoid cells from thymectomized, lethally-irradiated, bone marrow-reconstituted hamsters. Lymph node cells from such animals were killed by the anti-T cell serum only to the same extent as bone marrow cells, while spleen cells from these animals gave a good response to pokeweed mitogen but were virtually unresponsive to Concanavalin A. Passage of hamster spleen cells over nylon wool columns yielded effluent populations highly enriched in T lymphocytes. The eluted cells were fully capable of T ceil functions, as determined by their blastogenic response to various T and B ceil mitogens in vitro and their ability to inhibit the growth of syngeneic SV40 tumours in vivo. [ABSTRACT FROM AUTHOR]

Experiments were performed to investigate the influence of neonatal and adult splenectomy on humoral immunity in mice. In the bone marrow and lymph nodes of both groups of splenectomized mice the number of immunoglobulin (Ig)-positive (B) lymphocytes was significantly higher than in sham-operated mice. These higher numbers of B cells probably reflect a compensation for the absence of the B cell population of the spleen. Hardly any quantitative differences in the serum immunoglobulins were found between splenectomized and sham-splenectomized mice. Only for the IgM class was a significantly lower concentration found in the serum of splenectomized animals. This low concentration of IgM in the blood of splenectomized mice was caused by a failure of the remaining organs to compensate completely for the removal of the quantitatively important population of IgM producing plasma cells in the spleen. Nevertheless, the number of precursors of IgM-producing plasma cells in bone marrow and lymph nodes and their ability to differentiate into IgM-producing plasma cells was not diminished by splenectomy. Probably the spleen provides a highly efficient environment for the differentiation into IgM-producing plasma cells. By investigating the synergistic ability of bone marrow cells and thymus cells from neonatally splenectomized mice it was found that these cells were fully capable of co-operating in the adoptive plaque-forming cell response to sheep red blood cells (SRBC). [ABSTRACT FROM AUTHOR]

Radioautographic analyses were performed on PHA stimulated cultures of in vivo labelled cells obtained from mice previously injected with ³H-TdR to selectively label either cells with a rapid renewal rate (RR) or a slow renewal rate (SR). PHA responsive cells in the bone marrow (BM) were found to be virtually all RR cells, whereas both RR and SR cells from lymph nodes (LN) and spleen (Spl) were stimulated by this mitogen. However, RR cells were proportionately more responsive to PHA than SR cells in all tissues examined. Only one out of 200 BM PHA blasts belonged to the SR subclass, whereas the RR/SR ratio was approximately 1/1 for LN and 2/1 for Spl. Control experiments demonstrated that significant in vitro re-utilization of ³H-TdR from dying cells did not occur in the cultures. These results support a growing body of evidence that BM PHA responsive cells are precursor T-cells which are known to have a rapid turnover rate. [ABSTRACT FROM AUTHOR]

Antisera were prepared against a variety of chicken tissues with a view to detecting antigens specific for subpolpulations of T and B cells at different maturation stages. By appropriate absorption analysis, the following antigens were defined: (a) thymus organ-specific antigen (CTOA); (b) T lymphocyte-specific antigen (CTLA); (c) B lymphocyte-specific antigen (CBLA); (d) mature B lymphocyte-specific antigen (CBLA); (e) a foetal-associated antigen (CFAA) present on embryonic haemopoietic cells, and adult bone marrow and immature bursa cells, suggesting the cell types concerned may be at an early stage of development, possibly including precursors. For comparison with the above antigens, cells were also examined for surface Ig and IgG. T cells were found in periarteriolar sheaths in the spleen, and predominantly in the sub-epithelium and sub-mucosa of the caecal tonsil of the gut-associated lymphoid tissue (GALT). B cells were localized in periellipsoidal sheaths and germinal centers in the spleen, and in primary follicles or germinal centers in the GALT. The thymic and bursal medullas contained the mature populations of T and B lymphocytes respectively. [ABSTRACT FROM AUTHOR]

Describes the limited differentiation of mature T cell functions from mouse bone marrow in tissue culture. Comparison with similar differentiation occurring in vivo in irradiated bone marrow protected mice; Need for the re-interpretation of the data for regeneration of T lymphocytes in vitro from T-depleted sources in terms of the evidence for a pool of post-thymic precursors of T cells in such T-deficient cell populations.

Adult thymectomized, irradiated CBA mice were reconstituted with bone marrow and thymus grafts derived from congenic strains differing in immunoglobulin allotype. After challenge with heterologous erythrocytes the allotype of the antibody secreted by the chimaeric spleen cells was the same as that of the bone marrow donor. When mixtures of immune and non-immune cells from the two congenic strains were transferred to irradiated recipients, a preponderance of the immune-donor cells was found dividing in the recipients' spleen 3 days after challenge with the immunizing antigen, and the allotype of the antibody-producing cells 7 days after challenge was almost entirely of immune-donor derivation. Further quantitative studies on the number of mitotically reactive cells observed after immunization with heterologous erythrocytes indicate that after primary and secondary challenge the mitotic activity of these cells is increased respectively four and eight times relative to that found in unsensitized cells. [ABSTRACT FROM AUTHOR]

The occurrence of plaque-forming cells (PFC) in mouse bone marrow was studied during primary and secondary responses to the thymus-independent antigen Escherichia coli lipopolysaccharide (LPS). Anti-LPS responses were induced by various doses of LPS. During the primary response, doses of 1 and 10/μg LPS intravenously (i.v.) were found to evoke a distinct PFC response in both spleen and bone marrow. The spleen contained the majority of PFC until about 5 days after immunization. During the course of the reaction the number of PFC in the bone marrow rose to a level which equalled or surpassed the level in the spleen. LPS doses of 0.001, 0.01 and 0.1 μg i.v. only induced a PFC response in the spleen. Apparently there is a minimal threshold dose of LPS of about 1 μg for PFC to appear in the bone marrow. The secondary response was studied in mice primed with 1 μg LPS i.v. and boosted with either 0.001, 0.1 or 10 μg LPS i.v. 3 months later. After each dose tested the PFC activity in the spleen was several times higher than during the primary response. As was observed in the primary response doses of 0.001 and 0.1 μg LPS i.v. did not evoke a PFC response in the bone marrow. After boosting with 10 μg of LPS i.v. a significant PFC response was found in spleen, bone marrow, thymus, lymph nodes, Peyer's patches and blood. From about 5 days after the booster injection the number of PFC in the bone marrow exceeded the total number found in all other lymphoid organs. The results are discussed in relation to the bone marrow PFC response to the thymus-dependent antigen sheep red blood cells. To this antigen a clear PFC response in the bone marrow is found only during the secondary response. [ABSTRACT FROM AUTHOR]

Human lymphoid tissues and peripheral blood leucocytes and monocytes were studied with respect to the synthesis of complement components (Clq, C3 and C4) using an in vitro culture technique. All of the lymphoid tissues investigated (bone marrow, thymus, lymph node, spleen, tonsil, adenoid) synthesize complement components in different patterns. C3 was produced by all lymphoid tissues except the spleen, which was the only lymphoid tissue in which C4 production was regularly found. Clq synthesis was demonstrated in the spleen and adenoid cultures, and occasionally also in those of lymph node tissue. Lymphocytes in peripheral blood from normal individuals and in thoracic duct lymph, and also from patients suffering from chronic lymphatic leukaemia, do not synthesize any of these complement components. Peripheral blood leucocyte samples from normal individuals, containing 60 per cent lymphocytes and 40 per cent monocytes, do synthesize C3, however. Separation of the monocytes from these samples showed that it was in these cells that the synthesis of C3 occurred. Production of C3 by mononuclear phagocytes is also supported by the finding that peripheral blood leucocytes from patients suffering from acute monocytic leukaemia synthesize C3. Clq and C4 synthesis could not be demonstrated in any of the cultures of circulating leucocytes. [ABSTRACT FROM AUTHOR]

The patient's (Im) serum contained two myeloma proteins possessing the same heavy chains (γ1) and different light chains (κ or λ). The presence of identical antigenic determinants in the variable region of the heavy chains of both proteins raises the problem of their cellular origin. The immunofluorescence technique on bone marrow smears was used to identify the cells producing these proteins. Rabbit antisera monospecific to human κ and λ types of light chains, labelled with fluorescein or rhodamine, were applied onto the smears. These studies always revealed the presence of both κ and λ chains in the same plasma cells, thus suggesting that single cells of this patient are capable of synthesizing both IgGl (κ) and IgGl(λ) proteins. [ABSTRACT FROM AUTHOR]

Grain count histograms from autoradiographs of [³H]uridine-labelled rat thoracic duct lymphocytes confirm the previously reported difference in uridine uptake between thymus- and marrow-derived small lymphocytes in rats. This difference is used in conjunction with autoradiography to demonstrate the specificity of cytotoxic antisera distinguishing thymus- and marrow-derived small lymphocytes. Cytotoxic alloantisera detected a new polymorphic alloantigen system present on rat peripheral thymus-derived lymphocytes, but reduced or absent on thymocytes. At least three alleles or a complex genetic system are indicated. Rabbit antisera with specificity for rat marrow-derived small lymphocytes are described: these sera are not cytotoxic for haemolytic plaque-forming cells. [ABSTRACT FROM AUTHOR]

The functional integrity of the mononuclear phagocytic system (MPS) in mice infected with Trypanosoma brucei was investigated with regard to its possible significance in the aetiology of the immunosuppression characteristic of this disease. in infected mice the spleens and lymph nodes were grossly enlarged, and on histological examination it was shown that the MPS of the liver, lymph nodes, spleen and bone marrow was markedly expanded. Macrophages presented an active appearance and often contained cellular debris. Clearance of intravenously injected sheep red blood cells (SRBC) was increased, in that 1 hour after injection, 2-6 times more 51Cr-labelled SRBC had disappeared from the circulation of infected, compared to uninfected mice; this was due largely to an increased uptake by the expanded phagocytic system of the liver. The intrinsic immunogenic potential of individual macrophages appeared to be unimpaired as judged by the ability of SRBC-containing macrophages from infected mice to elicit a response in syngeneic normal recipient mice. It was concluded that the only evidence that immunosuppression might be associated with an altered activity of the MPS was an increased hepatic uptake of particulate antigen with a relative failure of splenic uptake. Together these might be responsible for a reduction in the concentration of antigen in the tissues of an enlarged spleen below the level necessary to initiate the formation of antibody. [ABSTRACT FROM AUTHOR]