Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 206, Issue 12, Pages 2659-2669Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20091087
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Funding
- Deutsche Forschungsgemeinschaft [Ku1315/4-1]
- Deutsche Jose Carreras Leukamie-Stiftung [R08/04]
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The origin of IgM(+)CD27(+) B lymphocytes with mutated IgV genes, which account for similar to 20% of human peripheral blood (PB) B cells, is controversially discussed. A generation in a primary diversification pathway, in T cell-independent immune responses, or in T cell-dependent germinal center (GC) reactions has been proposed. We show here that IgM(+)IgD(+)CD27(+) and IgM(+)IgD(-/low)CD27(+) B cell subsets carry, like class-switched memory B cells, mutations in the Bcl6 gene as a genetic trait of a GC experience. Moreover, the identification of PB IgM(+)IgD(+)CD27(+) B cells clonally related to GC-derived IgG(+) memory B cells with shared and distinct IgV gene mutations demonstrates the GC origin also of the former subset. These findings provide genetic evidence for a GC derivation of somatically mutated IgM(+) B cells and indicate that adult humans harbor a large population of IgM(+)IgD(+) post-GC memory B cells. Furthermore, the analysis revealed that a highly diverse and often very large population of memory B cells is generated from a given GC B cell clone, and that (preferentially IgM) memory B cells are generated already early in the GC reaction. This provides novel insights into the dynamics of GC reactions and the generation of a memory B cell repertoire.
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