Differential susceptibility of neonatal and adult murine spleen cells to in vitro induction of B-cell tolerance (original) (raw)
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Ontogeny of susceptibility of mouse splenic B cells to tolerance induction in vitro by TNP‐D‐GL
European Journal of Immunology, 1979
The susceptibility of mouse spleen cells to hapten‐specific tolerance induction of a primary in vitro thymus‐independent antibody response was examined. Both the induction of tolerance by 2,4,6‐trinitrophenyl‐D‐glutamic acid‐D‐lysine (TNP96D‐GL) and of antibody formation (elicited by TNP‐Brucella abortus) in neonatal spleen cell cultures were unaffected by anti‐Thy‐1.2 plus complement treatment. Spleen cells from neonatal mice were only slightly more sensitive to TNP96D‐GL tolerance induction than were cells from adult mice. The difference in susceptibility to tolerance induction was not nearly as great as that predicted by “clonal abortion”‐type theories of B cell tolerogenesis.
Journal of Experimental Medicine, 1977
The ease of tolerance induction in B lymphocytes from fetal, neonatal, and adult mice was studied in vivo, in a cell transfer system, and in vitro. Three different tolerogens were used: ultracentrifuged BGG, DNP(6)-D-GL, and ultracentrifuged DNP(22)-BGG. Irradiated thymectomized mice were reconstituted with B cells from fetal or neonatal liver or adult spleen or bone marrow. The mice were injected with tolerogen 1 day later. They were given normal thymus cells and challenged with either BGG or DNP(44)-BGG between 4 and 14 days after tolerance induction. With BGG no difference in ease of B-cell tolerance induction was observed in mice reconstituted with B cells from 17-day fetal liver, neonatal liver, 8- day-old spleen, adult spleen, or adult bone marrow. B cells from 14-day fetal donors are relatively resistant to tolerance induction. In contrast, with DNP(6)-D-GL and DNP(22)-BGG B cells from neonatal donors were clearly more susceptible to tolerance induction than were B cells from...
Journal of Experimental Medicine, 1977
During ontogeny IgD appears later than IgM on splenocytes of neonatal mice (1) and at a time when mice develop a markedly increased immune responsiveness (2). Based on these observations, it was suggested that IgD serves as a "triggering" isotype for induction of immune responses, whereas surface IgM functions as a tolerizing receptor (3). To test this hypothesis, the susceptibility of adult splenocytes (which are predominantly μ(+)δ(+)[4-6]) and neonatal splenocytes (which bear predominantly IgM [μp(+); 1, 4-6]) to tolerance induction were compared. The results indicate that neonatal splenic B cells responsive to thymus dependent (TD) antigens are exquisitely susceptible to tolerance induction compared with those from adult mice (7-9). However, cells from both adult and neonatal mice were highly susceptible to tolerance induction when thymus independent (TI) antigen was used as immunogen (8). These results suggest that the major precursor for the TD response is a μ(+)δ(+)...
The Journal of experimental medicine, 1975
Purified goat antibodies against mouse mu-chains and rabbit antibodies against mouse Ig determinants, and their Fab fragments, inhibited the development of IgM-bearing B cells in explant cultures of 14-day mouse fetal liver, and caused the disappearance of cell surface IgM in explant and dissociated cell cultures of more developed lymphoid tissues. While treatment of cultures of fetal or newborn liver, or adult bone marrow, with low concentrations (less than or equal to 10 mug/ml) of anti-Ig for less than or equal to 24 h caused the complete, but reversible, disappearance (modulation) of cell surface IgM, treatment for greater than or less than 48 h produced irreversible IgM suppression. In contrast, anti-Ig-induced suppression of cell surface IgM in cultures of adult spleen or lymph nodes required much higher concentrations of antibody (greater than or equal to 100 mug/ml) and was always reversible. These differences between immature and mature IgM-bearing cells could not be relate...
Tolerogenicity of resting and activated B cells
Journal of Experimental Medicine, 1994
Antigen presentation by resting splenic B cells has been shown previously to induce T helper 1 cell (Th1) anergy. In contrast to expectations, it was found here that B cells treated with F(ab')2 goat anti-mouse immunoglobulin (IgM) for 24 or 48 h also presented antigen (Ag) to Th1 cells in a manner that induced dramatic Ag-specific proliferative inactivation. The tolerogenicity of the anti-Ig-treated B cells was consistent with the observation that these B cells were only slightly more efficient than resting B cells in stimulating human gamma globulin (HGG)-induced proliferation of HGG-specific Th1 cells in primary cultures. The activated B cells were, however, more efficient than resting B cells in stimulating a primary mixed leukocyte reaction, and exhibited increased expression of major histocompatibility complex class II molecules, RL388 Ag and transferrin receptor. In addition, unlike resting B cells, which expressed little detectable B7, anti-Ig-treated B cells expressed h...
The Effect of Desensitization Protocols on Human Splenic B-Cell Populations In Vivo
American Journal of Transplantation Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2007
rabbit antithymocyte globulin (rATG) all have been suggested to have an effect on antibody producing cells, however, supporting data are lacking. To assess the impact of these agents on splenic B-cell populations in vivo, we retrospectively examined 25 spleens removed from patients treated with these agents as part of desensitization protocols in either ABO incompatible or positive crossmatch living donor kidney transplantation. These were compared to control (CTL) spleens removed for trauma. CTLs and spleens removed at transplant after multiple pretransplant plasmaphereses (PP) plus low-dose IVIG showed similar large numbers of naïve B cells (CD20 + and CD79 + ), plasma cells (CD138 + ) and memory B cells (CD27 + cells). Adding rituximab to this PP/IVIG regimen reduced the number naïve B cells, but had no effect on memory or plasma cells. Combination treatment (PP/IVIG, rituximab and rATG) showed a trend toward the reduction of CD27 + cells, but again plasma cells were unchanged. We conclude that none of these protocols reduces splenic plasma cells in vivo. PP/lowdose IVIG does not alter splenic B cells, but the addition of rituximab decreases mature B cells. Memory B cells may be affected by combination therapy including rATG and requires further study.
Journal of Experimental Medicine, 1976
Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent hapten-protein conjugate as well as by the inability of spleen cells from tolerant animals to respond to a thymus-independent hapten-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to thymus-dependent antigens does not affect B cells, but presumably only T cells. It is suggested that the only stringent test for the existence of B-cell tolerance is the inability of polyclonal B-cell activators to activa...
Susceptibility to Tolerance Induction of Bursal and Peripheral B Cells
Scandinavian Journal of Immunology, 1988
We investigated cellular aspects of immunological tolerance to protein antigens in chickens by examining the immune responses of bursal and splenic celis from tolerant or normal chickens after transfer into cyclophosphamide (CP)-trcated recipients. Newly-hatched chicks were made tolerant to bovine serum albumin (BSA) by injection of IIW mg of the antigen. When bursa cells from 4-day-old BSA-unresponsive chicks were transferred into C"P-trcated recipients, the reconstituted birds were able to respond to a subsequent injection of BSA almost as well as normal birds, iind as well as CP-treated birds that had been reconstituted wilh normal bursa cells. To investigate whether the presence of the BSA antigen might affect recovery from tolerance, we injected CP-treated recipients with BSA at the time of transfer of bursai cells. The presence of the tmtigen prevented the recovery of the anti-BSA response in reconstituted birds. When spleen cells from 6.5-week-oUf unresponsive chicks were transferred into CP-treatcd recipients, no recovery of responsiveness to BSA could be demonstrated. A likely reason for the failure of splenic B cells to recover responsiveness on transfer Is their inability to generate somatic variants of Ig genes in the same way as bursal stem eells. Thus, when the bursa involutes, the chicken's antibody repertoire may be frozen in a less adaptable stale thanihat ofa mammal.