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Treatment with anti-theta serum and the Wigzell column technique for cell separation was employed to study the separate functions of the B and T lymphocytes in the late states of immunity to the LCM virus in mice. The cell preparations examined were mixtures of spleen and lymph node cells from immune mice. The results revealed that the anti-viral effect of such cells after transfer to virus carriers was unimpaired in T cell-enriched and B cell-deprived cell preparations. The anti-viral effect was also retained in cell preparations deprived so much of B cells that no antibody was produced in the virus carrier mice receiving transplants of these cells. The results strongly indicate that the anti-viral effect of late immune cells is not only T cell-dependent but that it is also mediated solely by T cells and, moreover, that antibodies have no or very little influence on the virus elimination. The observation that antibody production could be caused neither by column-passed cells nor by anti-theta serum-treated cells, but was obtained by mixtures of these cells, demonstrates that co-operation between T and B cells is crucial for the LCM antibody response. Accordingly, the convincing demonstration of the absence in the persistent virus carriers of cells which, in respect of antibody production, are able to co-operate either with column-passed or with anti-theta serum-treated immune cells, implies that such animals are extremely deficient as regards immune function of both B and T LCM-primed lymphocytes. [ABSTRACT FROM AUTHOR]

The recovery of the B-cell population in adult thymectomized, BM mice) was studied. The irradiated and bone marrow-reconstituted mice T x number orb cells in the spleen of T × BM mice was estimated at various times after bone marrow transplantation. The spleen cells to be tested were mixed with dexamethasone-resistant thymocytes (DRT) and sheep red blood cells (SRBC) and transferred to irradiated recipients. The number of plaque-forming cells (PFC) in the spleen of the recipients was determined 7 days later. Using this functional B-cell assay a sequential appearance of the precursors of IgM-, IgGand IgA-PFC in the spleen of T × BM mice was observed. The precursors of IgM-PFC (IgM-B cells) were present immediately after transplantation. The first IgG-B cells could be detected at 13-16 days after transplantation and the IgAB cells finally appeared at 22 days after transplantation. The number of B cells reached a constant and normal level at 30 days after transplantation. The IgM-. IgG- and IgA-B cell development in sham-thymectomized, irradiated and bone marrow-reconstituted mice (ST × BM mice) was virtually the same as in T × BM mice. [ABSTRACT FROM AUTHOR]

The property of T cells to form rosettes with sheep red blood cells has been used to separate peripheral blood lymphocytes into purified T- and B-cell suspensions after density gradient centrifugation. A study of lymphocyte markers has shown that 2·6 per cern of E rosettes only were recovered in the B cell-enriched population. Lymphocyte stimulation in vitro was obtained with PHA. con A and PWM in unseparated and T-cell populations, but never in B-cell suspensions. Experiments of recombination between the two purified fractions have demonstrated that 10 per cent of T cells added to B cells were able to induce a response to PHA and PWM. Otherwise, only T cells responded to allogenic stimulation. Lastly, B and T cells seemed to bind qualitatively and quantitatively the same mitogens on their membranes. [ABSTRACT FROM AUTHOR]

Limiting dilution analysis has been applied to the study of T-cell 'helper' function in vitro. Using the microculture system one can estimate the numbers of (a) 'helper' T cells involved in specific collaboration with B cells and (b) those T cells which are able, on being activated by their specific antigen, to facilitate the response of B cells to another antigen. Such studies have enabled us to demonstrate that: (1) a single helper' T cell was able to activate a single B-cell precursor to detectable antibody production; (2) the `helper' function of primed T cells was radio-resistant; (3) a minimal estimate of `helper' frequencies could be obtained in defined cell populations; (4) non- specific facilitation was directed towards virtually all available B cells of a given specificity if these were challenged with their appropriate particulate antigen; (5) the microculture system offers the opportunity to determine whether specific and non-specific T-cell helper' effects are a consequence of the activity of one T-cell type or of different subpopulations of T cells. [ABSTRACT FROM AUTHOR]

Lymphocytes are heterogeneous with respect to their life-span. Typical B cells, bearing on their membranes immunoglobulin receptors, easily detectable by immunofluorescence, belong mainly to the long-lived population: this can be observed using combined autoradiography and immunofluorescence. However, when primed mice receive [³H]thymidine before a boosting injection of tobacco mosaic virus (TMV), many plasma cells appearing in the spleen during the secondary response are labelled. In irradiated recipients repopulated with spleen cells from donors primed with TMV and injected with tritiated thymidine 2 hours before killing, the majority of plasma cells appearing in the spleen after antigen injection were labelled. If irradiated mice were repopulated simultaneously with spleen cells from donors primed with TMV and injected with [³H]thymidine, and from donors primed with haemocyanin, most of the anti-TMV plasma cells were labelled, while most of the anti-haemocyanin plasma cells were unlabelled. These results allowed us to exclude non-specific reutilization of labelled thymidine as the main reason of our observations. It is concluded that either plasma cells derive from shortlived precursors or they receive material from a labelled cell able to co-operate specifically with plasma cell precursors. [ABSTRACT FROM AUTHOR]

Polymerized flagellin and E. coli lipopolysaccharide both express adjuvanticity in vivo and in vitro for responses to hapten conjugated to sheep crythrocytes, and hapten conjugated to soluble thymus-dependent antigens. In the case of erythrocyte-bound hapten, adjuvanticity is expressed in the absence of thymus-derived cells (T-cells). However, in the case of responses to soluble thymus-dependent conjugate, carrier-specific T cells would appear to be necessary for adjuvanticity to be expressed. On the basis of these observations on hypothesis for the mechanism of B-cell induction and tolerance is proposed. [ABSTRACT FROM AUTHOR]

By using T cell-deprived mice and appropriate controls it has been shown that the adjuvant activity of LPS on the immune response to different doses of SRBC, tends to be oriented more towards B cells than towards T cells. In contrast, lentinan seems to mediate its adjuvant activity largely through a stimulatory effect on helper T cells. [ABSTRACT FROM AUTHOR]

In an investigation of the immunosuppression associated with trypanosomiasis, the thymus-derived lymphocytes (T cells) and the thymus-independent lymphocytes (B cells) in mice with subacute Trypanosoma brucei infections were studied. It was shown that: (a) there was a massive plasma cell response in lymph nodes and spleen which replaced the thymus-dependent areas; (b) a failure of antibody production at the cellular level occurred as shown by the absence of IgM PFC responses to SRBC and lipopolysaccharide; (c) T cells appeared relatively normal as judged by their ability to proliferate following a primary stimulus with oxazolone unless measured during the terminal stages of the disease; (d) immune competence was rapidly restored after treatment with a trypanocidal drug. It appeared that immunosuppression was closely associated with the presence of living trypanosomes, possibly mediated through a B-cell defect. The mechanism whereby this might occur is discussed. [ABSTRACT FROM AUTHOR]

The induction in mice of a humoral immune response to intact sheep erythrocytes, both in vivo and in vitro, requires participation of thymus-derived (T) lymphocytes. In an in vitro system, spleen cells from both neonatally thymectomized and adult thymectomized irradiated bone marrow protected mice were successfully immunized, using washed sonicated sheep erythrocyte membrane fragments as antigen. This obviation of the requirement for T lymphocytes in the immune response, coupled with previous work on macrophage independence, indicates that sonicated membrane fragments were capable of directly immunizing bone marrow-derived (B) lymphocytes in vitro. These results further confirm the signal importance of antigenic structure in determining the cellular requirements for an immunological response; whereas antigens of particulate or monomeric form require the presence of both T cells and macrophages, polymeric antigens of intermediate size such as polymerized flagellin and sonicated sheep erythrocyte membranes require neither of these accessory cells. The results caution against the use of erythrocytes as models of thymus-dependent antigens. The data further suggest that reports of late antibody responses of relatively normal magnitude in thymectomized animals given larger doses of heterologous erythrocytes may have been due to direct immunization of B lymphocytes by degraded erythrocyte antigen. [ABSTRACT FROM AUTHOR]

Surface immunoglobulin can be demonstrated on almost all sheep erythrocyte rosette-forming cells in CBA and AKR mice, either by inhibition of antigen binding by anti-immunoglobulin or by immunofluorescence. When surface immunoglobulin on a rosette-forming cell is `capped' by anti-immunoglobulin, the bound red cells migrate with the immunoglobulin, demonstrating that the receptor-combining site and immunoglobulin antigenic determinants share the same mobile unit in the membrane. These observations strongly support the concept that the antigen receptor is surface immunoglobulin (at least for B cells), and illustrate the usefulness of the `capping' technique for studying the associations between membrane elements. [ABSTRACT FROM AUTHOR]

The capacity of CBA mouse B lymphocytes to bind polyvalent rabbit anti-mouse immunoglobulin antibody, even when this reagent is present in low concentration, was used as an index of a lymphocyte's B cell status. Various mouse tissues were held for 30 minutes at 0° with 0·2 μg/ml of 125I-labelled anti-Ig, and smear preparations of washed cells were examined, following radioautography, for their content of B cells. The survey covered two areas of B cell differentiation, namely the spontaneous emergence of B cells in the mouse foetus, and the development of B cells in lethally irradiated mice that had received early foetal liver as a source of haematogenous stem cells. The foetal survey suggested a multifocal origin of B cells, commencing 3 days before birth, in all major sites of erythromyelopoiesis, namely liver, spleen and bone marrow. Lymph nodes showed B cells later than did these organs, and thymus contained virtually no B cells at any stage. A rapid influx of B cells into lymph nodes took place shortly after birth. The CBA mouse is born with somewhat over 105 B lymphocytes in toto, of which the majority are in liver, spleen and blood. The irradiation-recovery study showed: (1) that B cells are, statistically, more sensitive to high dose irradiation than T cells; (2) that a B cell-free stem cell source can repopulate the B cell pool; (3) that repopulation is surprisingly slow; and (4) that numerical and functional recovery of B cells parallel each other to a reasonable degree. The significance of the results is discussed from the viewpoints of lymphocyte differentiation and immunological tolerance. [ABSTRACT FROM AUTHOR]

The immunological response to native levan (a fructose homopolymer with molecular weight 2 × 107) has been studied in (DBA/1 × CBA-T6T6)F1 mice by passive hemagglutination and plaque-forming cell (PFC) assays. It resembles type-specific pneumococcal polysaccharide (SSS) in eliciting a prolonged humoral antibody response over a wide dose range (0.0001-100 µg) and in inducing longlasting 'high zone' tolerance with a single injection (1 mg or more). Other similarities include an exclusively IgM response, independence of synergy with thymusderived lymphocytes and absence of immunological memory. On the other hand, parallelism between serum hemagglutinin and PFC levels following all doses of antigen implies that higher immunizing doses of levan, unlike SSS, do not engage in peripheral neutralization of antibody. It was concluded from studying the fate of 14C-labelled levan that this was attributable to more rapid elimination from the circulation and subsequent slow metabolism of this polysaccharide. Levan also differs from SSS in inducing tolerance directly, without a detectable prior immune phase. [ABSTRACT FROM AUTHOR]

Summary, OS chickens were subjected to bursectomy, thymectomy, bursectomyX-irradiation and bursectomy-X-irradiation followed by restoration with autoIogous bursa cells. The influence on the spontaneously occurring tbyroiditis was studied. Less pronounced tbyroiditis and thyroglobulin antibody formation was found in the bursectomized and bursectomized-irradiated but not in the thymectomized chickens. Bursectomized-irradiated chickens which had been reconstituted with autologous bursa cell suspensions showed total restoration of the thyroiditis No restoration of thyroglobulin antibody forming capacity and only partial restoration of immunoglobulin level was observed. The results suggest a dual function of the bursa with regard to thyroid autoimmunity in OS chickens, one humoral and possibly hormonal, which is essential for thyroglobulin antibody formation and one cellular which is necessary for the development of the inflammatory lesions in the thyroid gland. [ABSTRACT FROM AUTHOR]

The histogram of electrophoretic mobilities (EPM) of normal rat lymph node cells indicates a heterogeneous population. It can be resolved into two independent components with Gaussian distribution profiles. These two, Class 'A' cells and Class 'B' cells have different mean EPM. Their response in vivo to an antigenic stimuIation also appears to be different. Neither the mean EPM nor the relative concentration of 'B' cells shows any change. The mean EPM of 'A' cells also remains constant but their relative concentration decreases significantly with a concomitant emergence of a new cell type with a much lower mean EPM. The relative concentration of this new cell type varies with time but its kinetics parallels that of the circulating antibody titre. [ABSTRACT FROM AUTHOR]

Anti-allotypic sera that have no known allotypic determinants other than those also present in the genotype of the lymphocyte donor are as able to induce lymphocyte ‘blast’ transformation in vitro as are anti-allotypic sera that do have allotypic determinants that are not present in the lymphocyte donor. Therefore, anti-allotypic sera do not appear to function in the stimulation of blast transformation by providing access for any of the known allotypic determinants into lymphocytes. [ABSTRACT FROM AUTHOR]

Focuses on the collaboration between T- and B-cells in immunology. Mechanism of T-B-cell interaction; Nature of the T-helper cell receptor; Phase of B-cell differentiation.

Chickens depleted of both T and B cells were restored with T cells and with immature B cells capable of producing IgM only, and immunized with sheep red blood cells. These chickens developed strikingly few germinal centres, in marked contrast to controls which received normal adult B cells. [ABSTRACT FROM AUTHOR]

Highly purified resting tonsillar B lymphocytes mount an efficient mitogenic response on exposure to appropriate combinations of tumour-promoting phorbol esters and calcium ionophores, agents that mimic the biochemical second messengers generated through the cross-inking of surface immunoglobulins. By using agents that bind reversibly we show here that both signals need to be applied continuously in order for cells to proceed optimally to DNA synthesis. The data are consistent with the notion that, in the absence of 'help' from I lymphocytes or antigen-presenting cells, a chronic, persistent stimulation through antigen receptors is necessary to elicit a significant B-cell response. [ABSTRACT FROM AUTHOR]

Rat major histocompatibility complex (MHC) class II molecules RT1.Bl (DQ-like) and RT1.Dl (DR-like) were cloned from the LEW strain using reverse transcription–polymerase chain reaction and expressed in mouse L929 cells. The transduced lines bound MHC class II-specific monoclonal antibodies in an MHC-isotype-specific manner and presented peptide antigens and superantigens to T-cell hybridomas. The T-cell-hybridomas responded well to all superantigens presented by human MHC class II, whereas the response varied considerably with rat MHC class II-transduced lines as presenters. The T-cell hybridomas responded to the pyrogenic superantigens Staphylococcus enterotoxin B (SEB), SEC1, SEC2 and SEC3 only at high concentrations with RT1.Bl-transduced and RT1.Dl-transduced cells as presenters. The same was true for streptococcal pyrogenic exotoxin A (SPEA), but this was presented only by RT1.Bl and not by RT1.Dl. SPEC was recognized only if presented by human MHC class II. Presentation of Yersinia pseudotuberculosis superantigen (YPM) showed no MHC isotype preference, while Mycoplasma arthritidis superantigen (MAS or MAM) was presented by RT1.Dl but not by RT1.Bl. Interestingly, and in contrast to RT1.Bl, the RT1.Dl completely failed to present SEA and toxic shock syndrome toxin 1 even after transduction of invariant chain (CD74) or expression in other cell types such as the surface MHC class II-negative mouse B-cell lymphoma (M12.4.1.C3). We discuss the idea that a lack of SEA presentation may not be a general feature of RT1.D molecules but could be a consequence of RT1.Dlβ-chain allele-specific substitutions (arginine 80 to lysine, asparagine 82 to aspartic acid) in the extremely conserved region flanking the Zn2+-binding histidine 81, which is crucial for high-affinity SEA-binding. [ABSTRACT FROM AUTHOR]