Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells

被引:677
作者
Shapiro-Shelef, M
Lin, KI
McHeyzer-Williams, LJ
Liao, J
McHeyzer-Williams, MG
Calame, K
机构
[1] Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA
[2] Columbia Univ Coll Phys & Surg, Integrated Program Cellular Mol & Biophys Studies, New York, NY 10032 USA
[3] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
[4] Columbia Univ Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY 10032 USA
关键词
D O I
10.1016/S1074-7613(03)00267-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Blimp-1 is a transcriptional repressor able to drive the terminal differentiation of B cells into Ig-secreting plasma cells. We have created mice with a B cell-specific deletion of prdm1, the gene encoding Blimp-1. B cell development and the number of B cells responding to antigen appear to be normal in these mice. However, in response to either TD or TI antigen, serum Ig, short-lived plasma cells, post-GC plasma cells, and plasma cells in a memory response are virtually absent, demonstrating that Blimp-1 is required for plasmacytic differentiation and Ig secretion. In the absence of Blimp-1, CD79b(+)B220(-) pre-plasma memory B cell development is also defective, providing evidence that this subset is an intermediate in plasma cell development. B cells lacking Blimp-1 cannot secrete Ig or induce muS mRNA when stimulated ex vivo. Furthermore, although prdm1(-/-) B cells fail to induce XBP-1, XBP-1 cannot rescue plasmacytic differentiation without Blimp-1.
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页码:607 / 620
页数:14
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