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Extracts of human or calf thymus influence differentiation of human bone marrow cells in vitro. Incubation of a putative stem cell fraction of human marrow with extracts of thymus for a period of 2 hr led to the appearance of lymphocytes with surface antigens recognized by a highly specific anti-T-cell antiserum. To a lesser degree, development of lymphocytes having the capacity to form rosettes with sheep erythrocytes was observed. Treatment of the so-called stem cell fraction with thymic extracts did not yield cells responsive to mitogenic influences of phytohaemagglutinin or allogeneic cells. This model should permit further analyses of immunodeficiency diseases and provide a useful technique for purification and analysis of thymus extracts active with human haematopoietic cells. [ABSTRACT FROM AUTHOR]

An injection of a low dose of donor-type bone marrow cells causes specific added survival of skin allografts on antilymphocyte serum (ALS) treated mice over that seen in mice given only ALS. The effects of single injections of Bordetella pertussis, Bacillus Calmette-Guerin (BCG) and Cor ynebacterium parvum were studied at various times in this enhancing system. All three agents abrogated the prolongation when given 5 days after grafting but B. pertussis produced a striking increase in prolongation when given 7 days before skin grafting with ALS and subsequent bone marrow. This effect was not found with BCG or C. parvum. The unique graft-prolonging ability of B. pertussis may be related to the changes it produces in the regional nodes. [ABSTRACT FROM AUTHOR]

Mice infected with the nematode Trichinella spiralis or normal mice treated either with the serum of infected animals or with a parasite extract contained fewer spleen rosette-forming cells (RFC) to sheep erythrocytes than the controls, Bone marrow cells from infected mice were considerably less efficient than normal cells in reconstituting thymectomized, irradiated animals. [ABSTRACT FROM AUTHOR]

Rabbit appendix cells were injected into horses at weekly intervals, after which the horses were bled and the sera tested for cytotoxic activity. The unabsorbed antiserum was cytotoxic to the lymphocytes of all the lymphoid organs tested Following absorption with bone marrow and thymus cells, the antiserum lost all cytotoxic activity directed toward these cells but displayed almost undiminished cytotoxic activity toward the cells of the SAPP organs (sacculus rotundus, appendix and Peyer's patches). The absorbed antiserum also demonstrated cytotoxic activity toward certain lymphocytes present in the spleen, lymph node and circulation. Thus, the antibodies directed toward the antigens common to all lymphoid cells were removed by the thymus and bone marrow cells, leaving behind cytotoxic antibodies directed toss aid antigens present on appendix and appendix-derived cells only, We have therefore succeeded in preparing antisera specific for rabbit thymus, bone marrow and appendix cells, respectively. [ABSTRACT FROM AUTHOR]

Horse anti-rabbit bone marrow cell antiserum was tested for its cytotoxic activity with respect to the lymphocytes of the various lymphoid organs. The unabsorbed antiserum was highly cytotoxic with respect to the circulating WBC and cells of the bone marrow and thymus but demonstrated low cytotoxic activity with respect to spleen, lymph node and SAPP cells (sacculus rotundus, appendix and Peyer's patches). However, following absorption with thymocytes, lymph node cells or SAPP cells, cytotoxic activity directed toward any of these cell types disappeared without affecting the cytotoxic activity with respect to bone marrow and circulating lymphocytes. On the other hand, bone marrow and spleen cells and circulating white blood cells were capable of absorbing out completely the cytotoxic activity directed toward these cells, On the basis of a comparison of efficiency of absorption of anti-bone marrow cell activity by cells of the different lymphoid organs and cytotoxicity assays of the absorbed antiserum, it is concluded that approximately 15-25 per cent of the spleen lymphocytes and 20-40 per cent of the circulating lymphocytes in the rabbit are bone marrow-derived cells. The other lymphoid organs do not normally appear to possess these cells. [ABSTRACT FROM AUTHOR]

Defined cell populations representing limited periods in the erythropoietic sequence of adult chickens have been obtained by buoyant density centrifugation of bone marrow cells on bovine serum albumin gradients. The histones of these various populations and of circulating erythrocytes have been compared quantitatively by polyacrylamide gel electrophoresis. No change in the relative amounts of F1, F2a1, F2a2 (and possibly F3 + 2b), could be detected between the early polychromatic erythrocyte and the mature erythrocyte, although changes in the distribution of the F1 subfractions were observed. The amount of the erythrocyte specific histone (F2c), however, increases approximately 2.5-fold during this period. These events were correlated with a parallel decrease in RNA synthesis, both in whole cells and when measured in isolated nuclei. The results are discussed in relation to possible mechanisms of chromatin condensation and genome repression. [ABSTRACT FROM AUTHOR]

A 4 ½-month-old boy suffering from congenital severe combined immunodeficiency was successfully treated by transplantation of bone marrow-derived cells. His parents were cousins in the first degree. The donor was a 32-year-old maternal uncle, who was HL-A genotypically identical with the patient as was shown by serological typing and MLC. A stem cell rich fraction of the donor's bone marrow was prepared by albumin gradient centrifugation. The infant showed a full immunological reconstitution without any sign of GVH disease. Remarkably the only allotypic marker of his IgG which was different from the donor allotype remained in the serum after transplantation, and even showed an increase of its level. The infant was nursed in strict reverse isolation and his unfavourable endogenous microfiora of high potential pathogenicity was eliminated by antibiotic decontamination. [ABSTRACT FROM AUTHOR]

A comparative study of B cells present in human bone marrow and blood was performed. In both compartments the cells carrying the Ig receptors were found to be small mononuclear cells. Predominance of IgM receptors was found on bone marrow cells whereas Ig receptors present on peripheral blood cells were predominantly of the IgG class. Bone marrow lymphoid cells of non-sensitized donors were capable of binding a primary antigen, keyhole limpet haemocyanin (KLH) and could be retained on glass bead columns coated with either KLH or with goat anti-human IgM antiserum but not with anti-IgG. Whereas bone marrow cells of donors immunized with KLH 16-27 days earlier lacked KLH reactive cells, the latter cells could be demonstrated in the blood. It is concluded that human bone marrow B cells carrying IgM receptors are essential for the early antigen recognition step following which recruitment of these cells into the circulation takes place. [ABSTRACT FROM AUTHOR]

This article focuses on the recent observations and concepts in immunological unresponsiveness and autonomy. The establishment of immunological unresponsiveness in mice to deaggregated HGG requires approximately 4 days for completion, but 70, 85 and 92% of the cells are unresponsive after 6, 24 and 48 hours, respectively. Since thymus and bone marrow cells fail to reconstitute the immunocompetence of immediated mice to aggregated HGG if only one of the cell types is unresponsive, it was possible to study the kinetics of the induction of unresponsiveness separately in thymus and bone marrow cells.

The differences between the fate of mouse thymus and marrow cells labelled in vitro with [³H]adenosine following intravenous injection into syngeneic recipients are defined. Thymus cells home predominantly to the thymus-dependent territory in the recipient's peripheral lymphoid organs, whereas the majority of bone marrow cells is found in thymus-independent sites. In addition, it is shown that a marrow inoculum contains a variety of sub-populations able to discriminate microenvironmental differences within the thymus-independent territory itself in general, cell populations behave as if they have the ability to distinguish and home towards what is probably their usual environment. The word `ecotaxis' is offered to define this phenomenon, and the mechanisms that may be involved in determining it are discussed. [ABSTRACT FROM AUTHOR]

The clinical, immunologic and pathologic features of the first recorded examples of lymphopenic immunologic deficiency in twins are presented. Eleven-month-old male identical twin infants were found to be severely lymphopenic and lacked demonstrable cell-mediated immunity and antibody formation. Each first-degree relative differed from the probands by one chromosome at the major human histocompatibility locus, HL-A. Because of their rapidly deteriorating clinical conditions, allogeneic bone marrow transplantation was undertaken. Circumvention of graft-versus-host disease was attempted by separation of donor bone marrow cells on a discontinuous-albumin-gradient and administration of only 5 × 106 immature nucleated marrow cells per kilogram infant body weight. Additionally, immunologic enhancement was attempted by pretreating the infants with human isoantisera to identifiable infant HL-A antigens not present in the marrow donor. Paternal lymphocyte allografting occurred, as demonstrated by lymphocyte cytotoxicity testing, but both infants succumbed to graft-versus-host disease at the end of 3 weeks. [ABSTRACT FROM AUTHOR]

The cell types involved in the cellular immune response were studied with the GVH in vitro as a test system. Comparison of the activities of cells of different lymphoid organs in the GVH in vitro showed the cells of peripheral lymph glands and thoracic duct to be the most active. Second in activity were the cells from peritoneal exudate, mesenterial lymph nodes and spleen. Weak activity was found in thymus and bone marrow cells, whereas cells from Peyer's patches showed no activity at all. Treatment of donor animals with ATS, cortisone or cyclophosphamide simultaneously with (acceptor-) transplantation antigen, resulted in spleen cells which were less active in the GVH in vitro. No such results were obtained after treatment of donor animals with dimethylbenzanthracene or cyclo- phosphamide without antigen. Fractionation of donor spleen cells on a bovine serum albumin density gradient resulted in an accumulation of activity in one of the high density fractions (D), whereas this was reduced in the low density fractions (C, B and A) and absent in the highest density fraction (E). Separation of thymus cells on a glass bead column coated with transplantation antigen resulted in augmented activity of the adherent cell fractions, while the effluent cells were less active than the original cells. Fractionation of cells on an uncoated column resulted in adherent and non-adherent cells which were both inactive in the GVH in vitro. [ABSTRACT FROM AUTHOR]

Specific antisera reacting with mouse B and T lymphocytes were raised by immunizing rabbits with: (1) mouse myeloma tumour cells; (2) bone-marrow cells; (3) thymus cells, and proper absorptions of the antisera obtained. These antisera together with anti-IgG and anti-0 were used to characterize surface antigens on antibody-producing cells. It was found that anti-bone marrow serum, absorbed with thymus cells in the presence of guinea-pig C, completely inhibited in vitro the action of all types of antibody-producing cells, i.e. direct and indirect PFC, and normal and immune-RFC. Anti-myeloma serum absorbed with thymus cells inhibited direct and indirect PFC, most of the immune-RFC, but did not inhibit normal RFC. Absorption with both thymus and bone-marrow cells rendered the anti-myeloma scrum specific for an antigen present on PFC and myeloma cells (My antigen). Anti-IgG completely inhibited both normal and immune RFC but had only a minor inhibitory effect on PFC. On the other hand, antithymus absorbed with bone marrow cells, like anti-0, did not inhibit PFC, and occasionally inhibited a small percentage of RFC, With the aid of these betcrologous antisera at least three antigenic determinants could be defined on the surface of antibody-producing B lymphocytes: B1, B2 and My. Thus, normal-RFC were shown to be antigenically different from immune-RFC and both lack an antigen present in PFC. In addition, all these cells contained the B1 antigen, which was partially or completely missing from myeloma tumour cells. [ABSTRACT FROM AUTHOR]

The contribution of syngeneic bone marrow and thymus cell populations obtained from normal and cortisone-treated donor mice for reconstitution of delayed hypersensitivity to methylatcd human serum albumin (MHSA) was studied in lethally irradiated recipients employing a limiting dilution assay. Normal thymus cells contained at least one antigen-reactive cell (or cell unit) per 3.7 × 107 cells, while cortisone-resistant cell populations contained one cell per 6.7 × 105 cells. Thus, cells immunocompetent to MHSA are not destroyed by steroid. Bone marrow cell populations contribute effector cells, and as few as 2 × 106 cells are capable of fully restoring delayed response when combined with optimum numbers of thymus cells. Large numbers of thymus cells alone will restore immune responsiveness, indicating that such populations do contain some effector cells, either as contaminating blood borne cells, or as glandular cells derived possibly from sinusoids. Similarly, bone marrow cells in larger numbers restore responsiveness, implying contamination with thymus-derived cells. [ABSTRACT FROM AUTHOR]

Discusses the ability of thymus and bone marrow cells from immunized donors to restore antibody formation to BSA in irradiated mice. Determination of the effect of antigenic stimulation on the occurence of precursor cells in bone marrow and thymus; Focus on the difference of the frequency of thymic or bone marrow memory cells of a given specificity; Reconstitution of irradiated recipients with thymus and bone marrow cells from normal mice.

Bone marrow cells and thymus cells were observed in cell transfer expehments to collaborate in the production of anti-BSA antibodies. The target cells for tolerance induction either with a 'low dose' of antigen (100 µg of deaggregated BSA once a week × 5) or with a 'high dose' (a single injection of 5000 µg) were identified by the same technique. In 'low dose' tolerance, some indication was obtained that thymus-derived cells in peripheral lymphoid systems were the target cells; bone marrow-derived cells appeared not to be so susceptible, and the cells residing in thymus or bone marrow seemed to remain unimpaired, in contrast, the injection of a 'high dose' of tolerogen rendered both types of cells in spleen, thymus cells and bone marrow cells, unresponsive or hyporesponsive in parallel with one another. [ABSTRACT FROM AUTHOR]

The distribution of bone marrow-derived cells, thymus-derived cells and tissue-bound immunoglobulin was examined using indirect imrnunofluorescence. It was demonstrated that primary follicle small lymphocytes are bonemarrow derived in the absence of the thymus, they lack thymus-associated antigens, and bear high concentrations of surface-associated immunoglobulins. Thymusantigen positive cells make up the majority of, if not all, diffuse cortex lymphocytes, do not bear concentrations of surface immunoglobulin detectable in this system, are found as rare cells in primary follicles, and are present in germinal centres. A mechanism is proposed for the thymus-bone marrow interaction in the immune response. [ABSTRACT FROM AUTHOR]

The impaired antibody response of' neonatally bursectomized chickens was restored by bone marrow cells from normal—but not from bursectomized— syngeneic donors. Chimaerism of donor cells in the recipients was demonstrated using the sex chromosomal marker. Attempts to substitute autologous bursal cell suspensions for the bursa in situ were unsuccessful. It is concluded that B lymphocytes in chicken bone marrow have matured in the bursa. [ABSTRACT FROM AUTHOR]

Normal rat spleen cells, when cultured with solubilized sheep erythrocyte stroma in vitro, did not produce antibody but did show an increased rate of thymidine uptake. Normal rat bone marrow cells did not show a similar increase in thymidine uptake when cultured with solubilized stroma. Culture of these two cell types together with antigen resulted in a synergistic increase in thymidine uptake which decreased in intensity as the animals aged. The bone marrow population is responsible for this diminished synergistic activity. [ABSTRACT FROM AUTHOR]

Lethally-irradiated mice were injected with rat bone marrow cells and examined subsequently for the presence of rat macrophages, using an indirect fluorescent antibody test in conjunction with a fluorochrome-labelled phagocytic cell marker. Donor bone marrow cells were fractionated by (1) adherence, (2) magnetic removal of phagocytic cells containing ingested carbonyl iron and (3) treatment with lymphocyte-absorbed anti-rat macrophage serum either in vitro or in vivo. Extensive rat cell proliferation occurred in the resulting xenogeneic chimaeras by or after Day 4 and increased during the next week. The precursor of both the free and fixed macrophages was contained in the non-adherent, non-phagocytic population of bone marrow cells. The anti-macrophage serum was not selective and abolished the capability of bone marrow cells to proliferate. [ABSTRACT FROM AUTHOR]

The purpose of this investigation was to compare and contrast the migratory behaviour of three sub-classes of spleen lymphocytes in the mouse: cells capable of adsorbing a specific labelled antigen on to their surfaces ('antigenbinding' cells); bone-marrow-derived ('B') cells; and thymus-derived ('T') cells. Antigen-binding spleen cells were labelled in vitro with 125l-polymerized flagellin from Salmonella adelaide and injected intravenously into syngeneic recipients. Their distribution within the spleen was studied by radioautography for 24 hours after injection. Nearly all the antigen-binding cells localized and accumulated in and around the germinal centres of the white pulp. Bone-marrow-derived B-spleen cells which were labelled in vitro with ³H-uridine were found to localize in and around germinal centres. The proportion of B cells found in these regions was lower than the proportion of antigen-binding cells and there was not a progressive aggrregation of B cells over 48 hours. Thymus-derived T-spleen cells also labelled in vitro with ³H-uridine were located predominantly in the established thymus-dependent periarteriolar regions of the white pulp. The significance of the localization of antigen-binding cells in the germinal centre regions of spleen is discussed in relation to the B and T components of the spleen lymphocyte population. The conclusion was reached that B lymphoytes activated by contact with antigen Iodged preferentially in germinal centre areas. [ABSTRACT FROM AUTHOR]

Irradiated (NZB × BALB/c)F1 mice were injected with syngeneic bone marrow cells, syngeneic or parental thymus cells, and sheep red cells. The antibody plaque-forming cell response depended on the number of sheep cells and the age and strain of the thymus cells. Young or adult BALB/c thymus, and young hybrid thymus, responded best to low numbers of sheep cells; with higher numbers they became tolerant. Adult hybrid thymus, and young or adult NZB thymus, responded better to high numbers of sheep cells. Hybrid mice irradiated and restored with BALB/c bone marrow developed thymus cells with the reactivity of BALB/c thymus. It is argued that NZB mice, and older hybrids, may develop autoimmunity because of an abnormality of tolerance induction manifested in their thymus cells, but of bone marrow origin. [ABSTRACT FROM AUTHOR]

Previous studies have shown that thymectomized lethally irradiated bone marrow grafted mice, reconstituted with thymocytes and pretreated with a large dose of sheep red blood cells (SRBC), are unable to respond to a subsequent immunizing injection of SRBC even after an inoculation of normal thymocytes. If, however, the mice are not thymocyte reconstituted prior to the pretreatment with SRBC, they can respond almost normally to an immunizing injection of SRBC if inoculated with normal thymocytes after the termination of antigen pretreatment. In the present study the immunosuppressive effect of the presence of thymocytes during the antigen pretreatrnent was studied by adoptively transferring the spleen cells of the antigen pretreated mice to thymus-deprived chimeras. These spleen cells not only did not co-operate with normal thymocytes in the secondary hosts, but they also prevented the co-operation of normal thymocytes with normal bone marrow derived cells. Untreated spleen cells or treated spleen cells from mice not reconstituted with thymocytes did not affect cell co-operation in the secondary hosts. The abrogation of the co-operation in the secondary host was specific in that the addition of spleen cells did not affect the anti-horse red blood cell response, if the primary host made antibody as a result of the pretreatment, the transfer of their spleen cells did not prevent antibody production in the secondary host. [ABSTRACT FROM AUTHOR]

In mice infected with BCG the rate of development of resistance to L. monocytogenes was related, and the growth of BCG in the liver and spleen was inversely related, to the size of the infecting inoculum. The rate of elimination of BCG after the onset of immunity was independent of the infecting dose. The effect of dose on the growth of BCG in vivo was abolished by immunosuppressants, and was restored by certain categories of lymphoid cells. Spleen and thymus cells, but not bone marrow cells, were able to confer immunity on X-irradiated recipients. There was no evidence of co-operation between thymus and bone marrow cells. It is concluded that the inoculum effect in BCG infections has an immunological basis. With increasing doses of BCG there is progressive reduction of the latent period prior to the induction of immunity. [ABSTRACT FROM AUTHOR]

Bone marrow-thymus cooperation experiments were carried out in lethally irradiated mice with sheep red blood cells (SRBC) as the antigen and direct plaque-forming cells (PFC) as the end point. Various parameters were altered, with the following results: (1) Above 800 rad, the response by marrow cells alone, as well as the increase due to added thymus cells, was independent of irradiation dose. (2) The response of marrow cells was greatest at high SRBC concentrations, but the co-operative effect of thymus cells was most evident at lower SRBC levels, and completely absent at high levels. (3) Increasing the number of marrow cells, without thymus, gave increasing numbers of PFC, but the dose-response curve did not suggest cell synergism. (4) Thymectomy and antithymocyte serum treatment of host or donor did not prevent the response by marrow cells alone. It was concluded that this was a true IgM response by antibody-forming precursors from the marrow, unaided by thymus-derived cells. [ABSTRACT FROM AUTHOR]

CBA/H mice were lethally irradiated and treated with C57BL/H bone marrow cells. 8-14 days thereafter they were grafted under the kidney capsule with thymus derived either from CBA or from C57BL donors, 4-8 days old. Only 8 per cent of non-grafted animals survived 4 months, but 39 per cent of those grafted with CBA thymus, and 48 per cent of those grafted with C57BL thymus survived the same period. Grafted chimaeras of both groups had significantly more leucocytes in the peripheral blood, and more colony-forming units in the bone marrow, than chimaeras without a graft. A thymus graft syngeneic either with the donor or with the recipient of bone marrow improved the reactivityagainst bacterial antigens of Salmonella, but did not influence the reactivity against tissue antigens of sheep erythrocytes. It is concluded that immunological functions of allogeneic radiation chimaeras can not be restored entirely by stem cells from the bone marrow, but require normal (or even increased) cellular and humoral influence from non-irradiated thymus tissue as well. [ABSTRACT FROM AUTHOR]

The injection of polymerized flagellin into C57BL mice increased the number of granulocyte cluster-forming cells and macrophage colony-forming cells in the bone marrow. The addition of polymerized flagellin to agar cultures of bone marrow cells from normal or antigen-injected mice increased the number and growth rate of macrophage colonies developing when mouse serum was used as the source of colony stimulating factor (CISF). Polymerized flagellin had no potentiating effect on colony growth when urine or medium conditioned by bone marrow, spleen, lymph node or thymic cells were used as the source of CSF. Antigens may stimulate the proliferation of granulocyte and macrophage precursor cells by an indirect mechanism involving the production by bone marrow cells of CSF, or a similar growth promoting factor. [ABSTRACT FROM AUTHOR]

Mononuclear cells from various organs of sensitized donor rats were labelled in vitro with tritiated leucine and injected intravenously into sensitized, syngeneic recipients. The localization of injected cells was studied in radioautographs. Bone marrow cells were the most frequent of the labelled cells in skin reactions. Equal numbers of bone marrow cells were found in specific and non-specific delayed reactions and irritation reactions induced with turpentine. Lymph node cells were found in delayed but not in turpentine reactions. Spleen cells were less frequent than lymph node cells in delayed skin reactions; small numbers were found in the turpentine reactions. Lymph node and spleen cells did not show detectable antigenic specificity. Thymus cells were not found in the skin sites, even when they were allowed to circulate 2-3 days in the recipients before biopsies were taken. Irrespective of the source of the cells injected few or no labelled cells were found in the recipient thymuses. Lymph node and spleen cells migrated equally into lymph nodes and spleen, but were infrequent in bone marrow. Only bone marrow cells had a decided preference for their organ of origin. [ABSTRACT FROM AUTHOR]

The incorporation of some antigens such as bacterial endotoxin, heterologous erythrocytes and bacterial flagellin preparations can enhance the formation of colonies in cultures of normal mouse bone marrow or foetal liver cells in vitro. Other antigens such as foreign serum proteins and haemocyanin are inactive. This effect depends on the reaction of antigen with a component of normal mouse serum. [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]

It has been shown that intraperitoneal injection of Freund's complete adjuvant can stimulate the multiplication and effect the distribution within the animal of cells which form granulocytic and monocytic colonies in vitro. This response is associated with a leukocytosis and a fall in haematocrit. A variety of antigens were tested all of which resulted in an increase in the number of colony forming cells in the spleen to a greater or lesser degree. Two mechanisms are thought to be involved in this response: (1) with some antigens a direct stimulation of colony forming cells by an antigen-α-macroglobulin complex; and (2) an indirect stimulation of colony forming cells by release of colony stimulating factor from cells other than the colony forming cells. [ABSTRACT FROM AUTHOR]

Immunological memory and antibody formation appear to be properties of different cell fines. This follows from a demonstration that cells from spleens of mice primed with sheep erythrocytes are capable of inducing normally unresponsive bone marrow ceils to produce specific antibody. Primed spleen cells, taken from CBA or CBAT6T6 mice, were cultured for 5 or 6 days with an excess of bone marrow cells of the opposite chromosome type, and with antigen, in lethally irradiated, histocompatible mice. The tissue of origin of antibody-plaque-forming cells from the spleens of the irradiated mice was then identified from chromosome spreads of individual plaque-forming cells. After 5 days of culture, equal numbers of spleen and bone marrow cells were found producing antibody. At 6 days nearly all of the plaque-forming cells were from the bone marrow. Plaque-forming cells of bone marrow origin were also identified, using an immunogenetic technique, when semi-allogeneic mixtures of spleen and bone marrow cells were cultured together. [ABSTRACT FROM AUTHOR]

Results of the present experiments suggest that dividing cells in rat bone marrow can generate lymphocytes capable of initiating a systemic graft- versus-host reaction. In these experiments, Lewis bone marrow cells were incubated in vitro with either tritiated thymidine ([³H] thymidine) or 5-bromodeoxyuridine (BUDR)—agents which inhibit cell proliferation. Bone marrow cells prepared in this way and injected into an intermediate (Lewis × DA)F1 host were unable to pro-liferate and mature into circulating immunologically competent lymphocytes. Concentrations of [³H]thymidine and BUDR which inhibited the development of putative lymphocyte precursors in bone marrow had no obvious effect on the immunological performance of thoracic duct lymphocytes. Lewis lymphocytes, cultivated in medium containing these agents, caused a vicious graft-versus-host reaction in X-irradiated (Lewis × BN)F1 hybrid rats. The results strengthen the view that [³H]thymidine and BUDR exert their inhibitory effect on replicating lymphocyte precursors and not on long-lived members of the circulating lympho-cyte pool.

Peritoneal cells from non-immunized mice, when incubated in vitro with sheep red cells and complement in a film of carboxymethyl-cellulose gum, form plaques of haemolysis after a latent phase of 15–20 hours. Plaques are also produced by the free cells of the pleural cavity but not by lymph node, spleen, thymus and bone marrow cells. Plaques are not produced at room temperature, nor when the complement has been inactivated or the peritoneal cells have been heat-killed. The phenomenon is age-dependent: the peritoneal cells reach the highest activity when the donor mice are about 10 weeks old. By testing purified populations of lymphocytes and macrophages the cell type responsible for plaque production has been identified as the lymphocyte. Plaque formation is suppressed in the presence of an anti-mouse immunoglobulin serum without any detectable effect on cell viability or anticomplementary action. This suppressive effect is destroyed by prior precipitation of the antiserum with normal mouse serum. A technique which facilitates the study of peritoneal cells from individual mice has been developed and applied to peritoneal cells from Friend virus-infected mice. The activity of peritoneal cells 10 days after intravenous or intraperitoneal infection is similar to that of their uninfected counterparts. Peritoneal cells from mice killed 17 days after intravenous infection or 19 days after intraperitoneal infection form significantly reduced numbers of plaques. The reduced activity is accompanied by a decrease in the percentage of lymphocytes present in the peritoneal population of the infected mice. [ABSTRACT FROM AUTHOR]

The persistence of immunogenicity of lipopolysaceharide antigens of E. coli and of sheep red blood cells in the mouse was studied by a transfer system. Immunized mice were lethally irradiated and re-populated with non-immune syngeneic lymphoid and bone marrow cells at different times after immunization. Persistence of immunogenicity in the irradiated hosts was revealed as the induction of a primary immune response in the transferred cells. In this system SRBC persisted in an immunogenic form for 14 days whereas the bacterial antigens remained immunogenic for at least 45 days.

The ability of C57BL, C3H, and A strain marrow cells to proliferate on transplantation into irradiated isogenic, F1 hybrid, and backcross progeny mice has been investigated by the spleen-colony technique and by measuring the newly-formed DNA in the recipient spleen with [131I] 5-iododeoxyuridine. Transplants of C57BL cells grew poorly in (A × C57BL) F1 and in (C57BL × C3H) F1 and reciprocal hybrids, as compared with isogenic and allogeneic hosts, whereas C3H and A strain marrow grafts were successful in isogenic, F1 hybrid and backcross recipients. In segregating backcross progeny, i.e. in offspring from F1 hybrid females mated to C57BL males, the frequency of success or failure of the C57BL grafts suggested that the trait was controlled by a single pair of genetic determinants at an autosomal locus. The latter is apparently linked with, or part of, the H-2 region in the IXth linkage group. The experimental evidence suggested also that the failure of C57BL haemopoietic cell grafts in H-2 heterozygotes was not related to exhaustion of donor cells by excess of recipient isoantigen but rather to lack of expression in the heterozygotes of histocompatibility-related growth requirements yet undefined. These requirements are specific for haemopoietic cells, but not for skin grafts, and resulted most probably from the effect of genetic (inter-allelic) interaction involving H-2 or an H-2-linked locus. [ABSTRACT FROM AUTHOR]

Intensive treatment of 2-month old (NZB × NZW) F1 hybrid (BW) mice with antilymphocytic IgG (ALG) induced immediate renal disease, even when the mice were tolerant to rabbit IgG (NRG). Many of the features of the natural renal disease were present including glomerular hypercellularity with capillary narrowing and perivascular cellular infiltrates, but there was usually little evidence of immune complex deposition or of glomerular basement membrane (GBM) thickening as seen on immune fluorescence and electron microscopy, respectively. The induction of acute renal disease was prevented by syngeneic or allogeneic cell transfer, or by azathioprine. While moderate doses of ALG may suppress the Onset of renal disease in mice tolerant to NRG. it is suggested that excessive lymphocyte depletion encourages the proliferation of lymphoid cells and reticulum cells which are resistant to ALG treatment, but not to azothioprine, and may be under viral influence. Re-establishment of control over this process would account for the effectiveness of a graft of syngeneic, allogeneic or xenogeneic spleen, thymus and bone marrow cells. [ABSTRACT FROM AUTHOR]