Germinal center development

Abstract

Summary: 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 (Bml 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, Cμ to Cδ switch and preferential Igλ light chain usage: these cells may represent the precursors of normal and malignant IgD‐secreting plasma cells; iv) the centroblasis (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 sub‐populations showed that: i) programmed ceil 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‐hgation inhibits plasmacytic differentation 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.