摘要：

The Rockefeller University Press $30.00 J. Exp. Med. 2015 Vol. 212 No. 9 1465–1479 www.jem.org/cgi/doi/10.1084/jem.20150384 1465 B cell development is a complex process occurring in the fetal liver and then bone marrow. It begins with the proliferative expansion of progenitor cells that undergo sequential rearrangements of the Ig heavy chain (Igh) and Ig light chain (Igl) genes (Rajewsky, 1996; Meffre et al., 2000; Jung et al., 2006). Igh variable region exons are assembled from variable (VH), diversity (DH), and joining (JH) gene segments, a recombination process that must be tightly regulated to ensure lineage and stage specificity, as well as highly ordered; DH to JH joining occurs first in pre-pro–B cells, followed by VH to DHJH recombination in pro–B cells. Productive VHDHJH rearrangement results in the expression of a  heavy chain that assembles with the surrogate light chains (5 and VpreB) to form a pre–BCR, which defines the pre–B cell differentiation stage. After further clonal expansion, pre–B cells undergo rearrangement of VL and JL elements in the Igl loci, resulting in transition to the immature B cell stage, marked by the cell surface expression of an IgM BCR. Ultimately, cells expressing functional, nonselfreactive BCRs are positively selected into the peripheral pool of long-lived mature B cells. These CORRESPONDENCE Tomohiro Kurosaki: kurosaki@ifrec.osaka-u.ac.jp

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