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

• Published in: Seminars in immunology 1996-06, Vol.8 (3), p.169-177
• Main Authors: Liu, Yong-Jun, Arpin, Christophe, de Bouteiller, Odette, Guret, Christiane, Banchereau, Jacques, Martinez-Valdez, Héctor, Lebecque, Serge
• Format: Article
• Language: English
• Subjects: Adaptive immunology; Apoptosis; B-Lymphocytes - immunology; CD40 Ligand; germinal center; Germinal Center - physiology; Humans; Immunoglobulin Class Switching; Immunology; Immunotherapy; Innate immunity; isotype switch; Life Sciences; Membrane Glycoproteins - physiology; Mutation; Quantitative Methods; somatic mutation; Vaccinology
• ISSN: 1044-5323; 1096-3618
• DOI: 10.1006/smim.1996.0021

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 +, sIgD −CD38 +and sIgD −CD38 −B 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 +CD38 −B 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) SIgM −IgD +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) sIgD −CD38 +CD77 +B cells are centroblasts (Bm3), in which somatic mutation machinery is activated; (5) sIgD −CD38 +CD77 −B cells are centrocytes (Bm4), in which the isotype switching machinery is activated; (6) sIgD −CD38 −cells (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.