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.
引用
收藏
页码:607 / 620
页数:14
相关论文
共 57 条
  • [51] CDK inhibitor p18INK4c is required for the generation of functional plasma cells
    Tourigny, MR
    Ursini-Siegel, J
    Lee, H
    Toellner, KM
    Cunningham, AF
    Franklin, DS
    Ely, S
    Chen, MH
    Qin, XF
    Xiong, Y
    MacLennan, ICM
    Chen-Kiang, S
    [J]. IMMUNITY, 2002, 17 (02) : 179 - 189
  • [52] Characterization of the B lymphocyte-induced maturation protein-1 (Blimp-1) gene, mRNA isoforms end basal promoter
    Tunyaplin, C
    Shapiro, MA
    Calame, KL
    [J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (24) : 4846 - 4855
  • [53] BLIMP-1, A NOVEL ZINC FINGER-CONTAINING PROTEIN THAT CAN DRIVE THE MATURATION OF B-LYMPHOCYTES INTO IMMUNOGLOBULIN-SECRETING CELLS
    TURNER, CA
    MACK, DH
    DAVIS, MM
    [J]. CELL, 1994, 77 (02) : 297 - 306
  • [54] B cell-specific activator protein prevents two activator factors from binding to the immunoglobulin J chain promoter until the antigen-driven stages of B cell development
    Wallin, JJ
    Rinkenberger, JL
    Rao, S
    Gackstetter, ER
    Koshland, ME
    Zwollo, P
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (22) : 15959 - 15965
  • [55] YAN DH, 1995, MOL CELL BIOL, V15, P1901
  • [56] XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor
    Yoshida, H
    Matsui, T
    Yamamoto, A
    Okada, T
    Mori, K
    [J]. CELL, 2001, 107 (07) : 881 - 891
  • [57] Transcriptional repression by Blimp-1 (PRDI-BF1) involves recruitment of histone deacetylase
    Yu, J
    Angelin-Duclos, C
    Greenwood, J
    Liao, J
    Calame, K
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (07) : 2592 - 2603