Germinal center development.
Using a set of surface markers including IgD and CD38, human tonsillar B cells were classified into discrete subpopulations. Molecular and functional analysis allowed us to identify: i) two sets of naive B cells (Bm1 and Bm2); ii) germinal center founder cells (Bm2'); iii) an obscure population of germinal center B cells, displaying a high load of somatic mutations in IgV genes, C mu to C delta switch and preferential Ig lambda light chain usage: these cells may represent the precursors of normal and malignant IgD-secreting plasma cells; iv) the centroblasts (Bm3) in which somatic mutation machinery is activated; v) the centrocytes (Bm4) in which isotype switch occurs; vi) the memory B cells. The characterization of these subpopulations showed that: i) programmed cell death is set before somatic mutations, possibly providing an efficient way for affinity maturation; ii) only high affinity centrocytes are allowed to switch isotype; iii) CD40-ligation inhibits plasmacytic differentiation of mature B lymphocytes; iv) memory B cells preferentially differentiate into plasma cells; v) IgD isotype switch occurs in normal B cells; vi) receptor editing may be induced by somatic mutations in germinal centers. We also characterized two types of antigen-presenting cells in germinal centers: follicular dendritic cells that select high affinity B cells, and a new subset of germinal center dendritic cells that activate germinal center T cells.
Liu
Y J
YJ
Schering-Plough, Laboratory for Immunological Research, Dardilly, France.
Arpin
C
C
D000818:Animals; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D013601:T-Lymphocytes / Q000276:immunology