Scheeren Ferenc A, Nagasawa Maho, Weijer Kees, Cupedo Tom, Kirberg Jörg, Legrand Nicolas, Spits Hergen
Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
J Exp Med. 2008 Sep 1;205(9):2033-42. doi: 10.1084/jem.20070447. Epub 2008 Aug 11.
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.
外周血中IgM(+)IgD(+)CD27(+) B细胞被描述为循环边缘区B细胞。这些细胞何时以及在何处发育仍不清楚。这些IgM(+)IgD(+)CD27(+) B细胞在其B细胞受体中表现出体细胞超突变（SHM），但导致这些SHM诱导的信号的确切性质仍然难以捉摸。在这里，我们表明在人类胎儿发育过程中观察到携带SHM的IgM(+)IgD(+)CD27(+) B细胞。为了研究T细胞在人类IgM(+)IgD(+)CD27(+) B细胞发育中的作用，我们使用了一种体内模型，其中用人造血干细胞重新填充Rag2(-/-)gamma(C)(-/-)小鼠。在裸鼠背景下使用Rag2(-/-)gamma(C)(-/-)小鼠，我们证明人类IgM(+)IgD(+)CD27(+) B细胞的发育和SHM的诱导可以以不依赖T细胞的方式发生。
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