Ontogenic development of B-lymphocyte function and tolerance susceptibility in vivo and in an in vitro organ culture system.

Teale, Judy M.; Mandel, T. E.

doi:10.1084/jem.151.2.429

Cited by 31 publications

(13 citation statements)

References 29 publications

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“…The serum concentration of C5 (at 50 #g/ml) might be insufficient to induce B cell tolerance, though this concentration is known to induce B cell tolerance to heterologous gammaglobulin either in vitro (27,28) or in utero (29). Because it is known that neonatal cells are more susceptible than adult cells to tolerance induction (30) and because the C5sufficient mice had been exposed neonatally to C5, it is unlikely that the lack of B cell tolerance is due to the level of tolerogen. In autoimmunity, B cells are known to respond to autoantigens (31).…”

Section: Discussionmentioning

confidence: 99%

A natural model of immunologic tolerance. Tolerance to murine C5 is mediated by T cells, and antigen is required to maintain unresponsiveness.

Harris¹,

Cairns²,

Rosen³

et al. 1982

The Journal of Experimental Medicine

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A unique experimental model is described, where natural immunologic tolerance to a well-defined soluble native antigen (murine C5) is examined in congenic strains of mice that differ only by the presence or the absence of C5. A highly sensitive hemolytic assay was developed to detect nanogram amounts of C5 as well as an assay of anti-C5 inhibition of C5 hemolytic activity. The latter was more sensitive than immunodiffusion. Two reciprocal approaches were used to study the cellular basis of tolerance in irradiated hosts of either strain. In the first, lymphoid cells from either strain were transferred to irradiated B10.D2OSN hosts that were lacking C5 and so would not hinder detection of anti-C5 antibody upon challenge with murine C5. Second, lymphoid cells from either strain were transferred to irradiated B10.D2NSN hosts, whose native C5 provided the antigenic stimulus. The immune response of whole nonadherent spleen cell suspension as well as mixtures of T and B cells (separated on the basis of surface immunoglobulin) from either strain were studied. In addition, the duration of tolerance and the antigen requirement to maintain it in irradiated C5-deficient hosts repopulated with C5-sufficient spleen cells was examined. The positive control of irradiated C5-deficient hosts repopulated with syngeneic spleen cells showed a primary and secondary response to immunization. In contrast, C5-sufficient spleen cells failed to respond both in the primary and the secondary response. Because the unresponsiveness was not caused by antigen carryover and was not antigen specific, it represents central tolerance. In C5-sufficient irradiated hosts (where immunization was not required and antigen was present in natural form and physiological concentration), transfer of C5-deficient cells mediated a drop in C5 levels to 10-20% of that noted in unreconstituted controls. T and B cell mixing experiments from the two strains into deficient or sufficient hosts demonstrated that tolerance is T cell dependent and that C5-sufficient or -deficient B cells could cooperate with nontolerant C5-sufficient T cells to produce significant anti-C5 antibody or mediate a significant drop in C5 levels. In addition, the presence of antigen was necessary to maintain tolerance. In conclusion, these results show that (a) natural tolerance to C5 is an active process that is T cell dependent and requires the presence of antigen; (b) in this natural model, clonal abortion does not seem to occur; and (c) both tolerant and nontolerant B cells retain the capacity to produce autoantibody.

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Section: Discussionmentioning

confidence: 99%

A natural model of immunologic tolerance. Tolerance to murine C5 is mediated by T cells, and antigen is required to maintain unresponsiveness.

Harris¹,

Cairns²,

Rosen³

et al. 1982

The Journal of Experimental Medicine

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“…Ceci est en particulier vrai pour les lymphocytes B dont les cellules souches apparaissent d'abord dans la membrane vitelline, puis le foie (Moore et Metcalf, 1970 ;Paige et al, 1979) (Micklem et al, 1966). Des Pike, 1973 ;Owen et al, 1974 ;Bruyns et al, 1976 ; Andrew et Owen, 1978 ;Teale et Mandel, 1980 (Manning, 1975 ; Owen, 1983). Chez le rat, presque tous les lymphocytes B ne portent que de l'IgM de membrane à la naissance, toutefois, d'autre isotypes sont déjà détectables .…”

Section: Introductionunclassified

Ontogenèse et différenciation des lymphocytes B à IgE chez le rat

Manouvriez¹,

Bazin²

1984

Reprod. Nutr. Dévelop.

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“…The B cell repertoire in these studies is probed with the mitogen LPS and DNP, an antigen chosen because of its ability to stimulate B cells as early as 14 d of gestation (17,22) . The APCs that develop as a result of mitogen and antigen stimulation are analyzed for VH gene expression by in situ hybridization of single cells using prototype radiolabeled VH family probes .…”

mentioning

confidence: 99%

Comparison of the fetal and adult functional B cell repertoires by analysis of VH gene family expression.

Jeong

Teale

1988

The Journal of Experimental Medicine

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102

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The functional B cell repertoire in BALB/c mice was assessed at various stages in ontogeny. This was done by analyzing VH gene family expression using the sensitive technique of in situ hybridization. The B cell repertoire was probed with the mitogen, LPS, and the antigen DNP. DNP was chosen because B cells responsive to this hapten appear very early in ontogeny. The APCs that developed after stimulation with LPS or DNP were analyzed for VH gene expression by in situ hybridization of individual cells using radiolabeled VH gene family probes. The results indicated that VH gene expression in fetal B cells after stimulation was distinct from adult B cells in that there was a biased expression of D proximal families. The results indicated that this bias was associated with developmental age and not a given differentiation stage in the B cell lineage. In addition, stimulation of fetal B cells with DNP resulted in a large increase in expression of member(s) of VH 36-60, suggesting that the early appearance of DNP-responsive B cells is not strictly correlated with preferential rearrangement of D proximal families, VH 7183 and VH Q52. However, the results suggested that a large proportion of pre-B cells that preferentially rearrange D proximal families early in ontogeny become part of the functional developing repertoire.

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Ontogenic development of B-lymphocyte function and tolerance susceptibility in vivo and in an in vitro organ culture system.

Cited by 31 publications

References 29 publications

A natural model of immunologic tolerance. Tolerance to murine C5 is mediated by T cells, and antigen is required to maintain unresponsiveness.

A natural model of immunologic tolerance. Tolerance to murine C5 is mediated by T cells, and antigen is required to maintain unresponsiveness.

Ontogenèse et différenciation des lymphocytes B à IgE chez le rat

Comparison of the fetal and adult functional B cell repertoires by analysis of VH gene family expression.

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