Elsevier

Seminars in Immunology

Volume 8, Issue 3, June 1996, Pages 169-177
Seminars in Immunology

Regular Paper
Sequential triggering of apoptosis, somatic mutation and isotype switch during germinal center development

https://doi.org/10.1006/smim.1996.0021Get rights and content

Abstract

Using an approach similar to that used to study primary B-lymphocyte development within bone marrow and primary T-lymphocyte development within thymus, the peripheral B-cell maturation pathway within secondary lymphoid tissue (human tonsils) was analysed on the expression of discrete surface antigens. sIgD and CD38 permit the identification of four subpopulations of tonsillar B lymphocytes, including sIgD+CD38, sIgD+CD38+, sIgDCD38+and sIgDCD38B cells. Further phenotypic, functional and Ig gene analysis (IgV gene sequences, expression of sterile transcripts and DNA switch circles) allowed us to conclude the following: (1) sIgM+IgD+CD38B cells are naive B cells (BM1+2), which carry unmutated antigen-receptors; (2) sIgM+IgD+CD38+B cells are germinal center founder cells (BM2′), which become prone to undergo apoptosis before the onset of somatic mutation; (3) SIgMIgD+CD38+are germinal center B cells (Bm3δ), that have accumulated the highest number of somatic mutations ever reported in normal B cells; these cells may have undergone Cμ-deletion by homologous recombination through σμ-Σδ sequences: (4) sIgDCD38+CD77+B cells are centroblasts (Bm3), in which somatic mutation machinery is activated; (5) sIgDCD38+CD77B cells are centrocytes (Bm4), in which the isotype switching machinery is activated; (6) sIgDCD38cells (Bm5) represent somatically mutated resting memory B cells. In conclusion, human peripheral B-cell subpopulations corresponding to the differentiation stages before, during and after the triggering of apoptosis program, somatic mutation and isotype switch have been identified and isolated using a combination of surface markers.

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