Blimp-1 is required for the formation of immunoglobulin secreting plasma cells and pre-plasma memory B cells.
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.
Shapiro-Shelef
Miriam
M
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Lin
Kuo-I
KI
McHeyzer-Williams
Louise J
LJ
Liao
Jerry
J
McHeyzer-Williams
Michael G
MG
Calame
Kathryn
K
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D007156:Immunologic Memory / Q000502:physiology*; D051379:Mice; D010950:Plasma Cells / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000502:physiology*; D017422:Sequence Analysis, DNA; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; C513258:Prdm1 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1