Differences in susceptibility of mature and immature mouse B lymphocytes to anti-immunoglobulin-induced immunoglobulin suppression in vitro. Possible implications for B-cell tolerance to self.

Raff, Mc; Owen, J. J. T.; Cooper, Max D.; Lawton, Alexander R.; Megson, Matthew; Gathings, William E.

doi:10.1084/jem.142.5.1052

Cited by 213 publications

(85 citation statements)

References 28 publications

(35 reference statements)

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“…One of the grounds for their abortive theory of immunological tolerance is the finding that immature B cells exposed in vitro to an antigen did not generate AFC specific for the antigen upon stimulation with LPS. Findings that immature B cells were unable to reexpress s-Ig receptors after being removed by anti-Ig (23,25) and antigen (4), whereas adult B cells easily reexpressed s-Ig receptors after these procedures, may support this idea. In tolerance in mature B cells, Fidler reported the occurrence of B cell elimination.…”

Section: Time Kinetics Of Induction Of and Recovery From Tolerancesupporting

confidence: 60%

B Cell Tolerance

Uchiyama

1980

Microbiology and Immunology

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The mechanisms of B cell tolerance were studied in an attempt to learn whether B cells rendered tolerant are present in the immune system in a potentially responsive form. The author tested the in vitro anti‐trinitrophenyl (TNP) antibody‐forming cell (anti‐TNP AFC) response to TNP‐immunogens and polyclonal B cell activators (PBA) of spleen cells taken from mice injected with a tolerogen, TNP‐carboxymethylcellulose (TNP‐CMC). Spleen cells from mice injected 5 days previously with 10 μg of TNP‐CMC did not respond to TNP‐sheep red blood cells (TNP‐SRBC), T‐dependent (TD) antigen or TNP‐Ficoll, T‐independent (TI) antigen. However, the same spleen cells responded to PBA, lipopolysaccharide (LPS) of Salmonella enteritidis and purified protein derivative (PPD) of BCG. The results indicate that B cells specific for TNP are present in a potentially responsive form. Spleen cells from mice injected with 500 μg of TNP‐CMC did not respond to either TNP‐immunogens or PBA. The state of unresponsiveness to PBA lasted for 12 days after the tolerogen injection. Responsiveness to PBA reappeared within the short period of 2 days, whereas unresponsiveness to TNP‐immunogens lasted much longer. Unresponsiveness to PBA was relieved considerably by treating tolerant spleen cells with the proteolytic enzyme trypsin before in vitro stimulation. These results indicate that B cells rendered refractory are present in the immune system in a potentially responsive form.

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Section: Time Kinetics Of Induction Of and Recovery From Tolerancesupporting

confidence: 60%

B Cell Tolerance

Uchiyama

1980

Microbiology and Immunology

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“…2A), a phenotype that we and others have attributed to continual Ag encounter (17,18,30,(35)(36)(37)(38)(39)(40)(41)(42). At all ages examined, anti-dsDNA B cells from VH3H9 BALB-lpr/lpr mice had increased levels of B220, as compared with Fas-sufficient VH3H9 BALB/c mice (Fig.…”

Section: Altered Localization and Cell Surface Phenotype Of Anti-dsdnmentioning

confidence: 99%

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

Fields

Sokol

Eaton-Bassiri

et al. 2001

The Journal of Immunology

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Autoantibodies directed against dsDNA are found in patients with systemic lupus erythematosus as well as in mice functionally deficient in either Fas or Fas ligand (FasL) (lpr/lpr or gld/gld mice). Previously, an IgH chain transgene has been used to track anti-dsDNA B cells in both nonautoimmune BALB/c mice, in which autoreactive B cells are held in check, and MRL-lpr/lpr mice, in which autoantibodies are produced. In this study, we have isolated the Fas/FasL mutations away from the autoimmune-prone MRL background, and we show that anti-dsDNA B cells in Fas/FasL-deficient BALB/c mice are no longer follicularly excluded, and they produce autoantibodies. Strikingly, this is accompanied by alterations in the frequency and localization of dendritic cells as well as a global increase in CD4 T cell activation. Notably, as opposed to MRL-lpr/lpr mice, BALB-lpr/lpr mice show no appreciable kidney pathology. Thus, while some aspects of autoimmune pathology (e.g., nephritis) rely on the interaction of the MRL background with the lpr mutation, mutations in Fas/FasL alone are sufficient to alter the fate of anti-dsDNA B cells, dendritic cells, and T cells.

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“…To examine this proposition, the response of splenic B cells from neonatal mice was analyzed. Neonatal spleens are presumably enriched in immature, developing cells and have been demonstrated to be highly susceptible to suppression by anti-immunoglobulin (23)(24)(25) or anti-idiotypic antibodies (26). The results in the present study indicate that B cells, early in their development, are readily tolerized in vitro in a highly specific manner, by low concentrations of hapten on a wide array of carriers, while the vast majority of adult splenic B cells remain unaffected by antigen at these concentrations and concentrations which are four orders of magnitude greater.…”

Section: Antigen Concentration and Carrier Independence Of Tolerance mentioning

confidence: 99%

“…Recent comparative studies of neonatal and adult B cells have demonstrated differences in susceptibility to anti-immunoglobulin or anti-idiotype antibody-induced suppression (23)(24)(25)(26), implying that neonatal (i.e., immature or developing) cells may be highly susceptible to tolerance induction. In addition, Nossal and Pike have demonstrated that developing B cells in the adult bone marrow may indeed be susceptible to tolerance induction (27).…”

mentioning

confidence: 99%

In vitro tolerance induction of neonatal murine B cells.

Metcalf¹,

Klinman²

1976

The Journal of Experimental Medicine

263

149

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Immunologic tolerance was originally defined as specific hyporesponsiveness to an antigen which results from prior contact with that antigen (1, 2). The concept of natural tolerance to self-antigens was perceived by Burnet (3) as the deletion of clones reactive to autologous antigens after contact of these antigens with the reactive cells' specific antigen receptors during the development of the cell's immunologic competence. If such a theory were to have physiological relevance, then several predictions should be realized: (a) developing cells should be significantly more susceptible to tolerance induction than their mature counterparts; (b) tolerance should be inducible over a wide range of antigen concentrations, since the concentrations of different self-antigens present presumably vary; (c) since the spectrum of self-antigens is diverse, the development of unresponsiveness should be plausible with a wide variety of antigenic structures; (d) since bone marrow-derived precursors to antibody-forming cells (B cells) presumably mature independently of other cell types, induction of B-cell tolerance should occur in the absence of antigen-specific thymus-derived lymphocytes (T cells); (e) the discrimination between self and nonself would be absolute, and therefore, tolerance should exhibit exquisite determinant specificity.

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Differences in susceptibility of mature and immature mouse B lymphocytes to anti-immunoglobulin-induced immunoglobulin suppression in vitro. Possible implications for B-cell tolerance to self.

Cited by 213 publications

References 28 publications

B Cell Tolerance

B Cell Tolerance

Fas/Fas Ligand Deficiency Results in Altered Localization of Anti-Double-Stranded DNA B Cells and Dendritic Cells

In vitro tolerance induction of neonatal murine B cells.

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