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

Scheeren, Ferenc A.; Nagasawa, Maho; Weijer, Kees; Cupedo, Tom; Kirberg, Jörg; Legrand, Nicolas; Spits, Hergen

doi:10.1084/jem.20070447

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Journal article

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

Scheeren, Ferenc A. Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Nagasawa, Maho Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Weijer, Kees Netherlands Cancer Institute–Antoni van Leeuwenhoek Ziekenhuis, 1066 CX Amsterdam, Netherlands
Cupedo, Tom Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands
Kirberg, Jörg University of Lausanne, Department of Biochemistry, 1066 Epalinges, Switzerland
Legrand, Nicolas Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
Spits, Hergen Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands

2008-8-11

Published in:

Journal of Experimental Medicine. - Rockefeller University Press. - 2008, vol. 205, no. 9, p. 2033-2042

English 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.

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