Expression of specific clones during B cell development

109

The process by which an individual's repertoire of unique antibody-forming cell precursor (B-cell)' specificities (clonotypes) is acquired has been the subject of extensive investigation and controversy over the past several years (1-3) . To help clarify the mechanism by which diversification of B-cell clonotypes might occur, this laboratory has conducted an investigation of the B-cell clonotypes available during the early stages of neonatal development, i .e ., at an important period in the initial development of the specificity repertoire .Previous reports from this laboratory have demonstrated that the adoptive transfer of neonatal spleen cells to an adult, carrier-primed environment maximizes the responsiveness of neonatal B cells (4-6) . The principle rationale for this approach-that neonatal B cells are indeed immunologically competent when provided with ancillary mechanisms by the adult host environment-has been verified by other investigators (7,8) . Previous analyses from this laboratory have also shown the similarity of neonatal and adult primary B cells, in terms of the kinetics and antigen dose dependence of the antibody response (4), and the relative ease of hapten inhibition of primary B-cell stimulation (6,9,10) . Recently, an analysis of the frequency of neonatal B-cell precursors specific for the haptenic determinants 2,4-dinitrophenyl (DNP) ; 2,4,6-trinitrophenyl (TNP) ; and fluorescein (FL) has demonstrated that a disparity exists in the rate of development of FL-specific precursor cells, as compared to DNP-or TNP-specific cells (5) . Thus, at an early stage in the generation of specificity, when the total number of available specificities is limited, significant disparities may exist due to potential "all or none" expressions .This report extends these observations by an analysis of the clonotypes available in neonatal BALB/c mice which are specific for the DNP and TNP haptenic *

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 84%

See 3 more Smart Citations

The characterization fo the B-cell repertoire specific for the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl determinants in neonatal BALB/c mice.

Klinman¹,

Press²

1975

109

In vitro tolerance induction of neonatal murine B cells.

Metcalf¹,

Klinman²

1976

263

149

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.

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

Jeong

Teale

1988

102

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.