Ontogeny of susceptibility of mouse splenic B cells to tolerance induction in vitro by TNP‐D‐GL (original) (raw)
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Journal of Experimental Medicine, 1976
The relative susceptibility of neonatal and adult murine splenocytes to induction of B-cell tolerance was studied in vitro. Adult cells required approximately 1,000-fold more trinitrophenyl-human gamma globulin to be rendered tolerant than did cells from 9- to 12-day-old neonates. The potential effects of suppressor T cells were excluded by pretreating the cultured B cells with anti-Thy-1 and C' and the helper T cells with anti-Ly-2.2 and C'. The possible role of cell surface immunoglobulin isotypes in contributing to this observed difference is discussed.
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(+)...
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...
Immunology, 1984
CBA/N mice harbour an X-linked B cell defect which is transmitted by CBA/N female mice to their hybrid male progeny. These mice mount normal responses to thymus-dependent (TD) and some thymus-independent (TI-1) antigens, while the response to TI-2 antigens is absent. Hapten-specific plaque-forming cell (PFC) responses to TD antigens can be blockaded by concomitant exposure of these mice to TI-2 antigens bearing the same hapten. This paper investigates in defective mice the blockade of their response to TNP3-LPS (trinitrophenylated lipopolysaccharide, a TI-1 antigen), imposed by DNP59-Ficoll (dinitrophenylated Ficoll, a TI-2 antigen). The effectiveness of the blocking agent, DNP59-Ficoll, differed in various inbred mouse strains: CBA/N X C3H/HeN F1 male greater than CBA/N female greater than CBA/N X C3H/HeN F1 female. The role of T cells in the observed hapten-specific blockade phenomenon was investigated using athymic CBA/N nude mice and a B cell tolerogen. Our findings indicate tha...
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...
European Journal of Immunology, 1978
Brucella abortus and to trinitrophenyl (TNP) conjugates of Brucella abortus CBA/N mice have an X-linked immune defect in B lymphocyte function which leads t o their inability to respond to several thymus-independent antigens. We report here that these mice and immunologically defective F1 male CBA/N x DBA/2N) mice can respond t o Brucella abortus and t o 2,4,6-trinitrophenyl derivatives of Brucella abortus (TNP-BA). These responses can b e obtained in vivo and in vitro and are thymus-independent b y the criteria that (a) they can be transferred t o irradiated recipients b y bone marrow cells and anti-Thy-1.2 and complement-treated spleen cells; (b) that nu/nu BALB/c spleen cells respond t o TNP-BA in vitro; and (c) that anti-Thy-1.2 and complement-treated (CBA/N x DBA/2N)F1 male spleen cells respond t o TNP-BA in vitro. B. abortus and TNP-BA are poor polyclonal B cell activators (PBA) and poor B cell mitogens, unlike lipopolysaccharide which is both a powerful PBA and B cell mitogen. These results therefore indicate that mice with the CBA/N B cell defect can respond t o some thymus-independent antigens, namely TNP-BA, and as shown previously, TNP-LPS, although not to other thymus-independent antigens. This, in turn, suggests that thymus-independent antigens may be subdivided o n the basis of their ability or inability t o stimulate responses by CBA/N B lymphocytes.
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.