T cell–independent development and induction of somatic hypermutation in human IgM+IgD+CD27+ B cells

• DOI: 10.1084/jem.20070447
• Publication Date: 2008-08-12T00:45:09Z
• Authors: Ferenc A. Scheeren; Maho Nagasawa; Kees Weijer; Tom Cupedo; Jörg Kirberg; Nicolas Legrand; Hergen Spits
• Keywords: Mice, Knockout; 0301 basic medicine; B-Lymphocytes; Mice, Inbred BALB C; T-Lymphocytes; Mice, Nude; Articles; Immunoglobulin D; Fetal Blood; Hematopoietic Stem Cells; Tumor Necrosis Factor Receptor Superfamily, Member 7; Mice; 03 medical and health sciences; Immunoglobulin M; EMC MM-02-41-04; Mutation; Animals; Humans; Signal Transduction

IgM+IgD+CD27+ B cells from peripheral blood have been described as circulating marginal zone B cells. It is still unknown when and where these cells develop. These IgM+IgD+CD27+ B cells exhibit somatic hypermutations (SHMs) in their B cell receptors, but the exact nature of the signals leading to induction of these SHMs remains elusive. Here, we show that IgM+IgD+CD27+ B cells carrying SHMs are observed during human fetal development. To examine the role of T cells in human IgM+IgD+CD27+ B cell development we used an in vivo model in which Rag2−/−γC−/− mice were repopulated with human hematopoietic stem cells. Using Rag2−/−γC−/− mice on a Nude background, we demonstrated that development and induction of SHMs of human IgM+IgD+CD27+ B cells can occur in a T cell–independent manner.