The Journal of Experimental Medicine
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Published online August 11, 2008
doi:10.1084/jem.20070447
The Journal of Experimental Medicine, Vol. 205, No. 9, 2033-2042
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Scheeren et al.
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ARTICLE

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

Ferenc A. Scheeren1, Maho Nagasawa1, Kees Weijer1,2, Tom Cupedo3, Jörg Kirberg4, Nicolas Legrand1, and Hergen Spits1

1 Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands
2 Netherlands Cancer Institute–Antoni van Leeuwenhoek Ziekenhuis, 1066 CX Amsterdam, Netherlands
3 Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands
4 University of Lausanne, Department of Biochemistry, 1066 Epalinges, Switzerland

CORRESPONDENCE Hergen Spits: spits.hergen{at}gene.com

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–/–{gamma}C–/– mice were repopulated with human hematopoietic stem cells. Using Rag2–/–{gamma}C–/– 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.

Abbreviations used: AID, activation-induced cytidine deaminase; HIS, human immune system; HSC, hematopoietic stem cell; MLN, mesenteric lymph node; MZ, marginal zone; SHM, somatic hypermutation; shRNA, short hairpin RNA.

F.A. Scheeren's present address is Stanford University School of Medicine, Stanford, CA 94305.

H. Spits' present address is Genentech, South San Francisco, CA 94080.

© 2008 Scheeren et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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