Blimp-1 overcomes the block in IgM secretion in lipopolysaccharide/anti-mu F(ab')2-co-stimulated B lymphocytes.
A combination of signals transmitted through the antigen receptor, membrane-bound cell interaction molecules and cytokine receptors induces B cell proliferation and differentiation into immunoglobulin-secreting or memory cells. It has recently been suggested by Turner et al. (Cell 1994. 77: 297) that the complex changes in gene activities accompanying high levels of immunoglobulin secretion are under the common control of a master regulator, Blimp-1 (B lymphocyte-induced maturation protein). We show here that in naive mouse B cells stimulated with lipopolysaccharide (LPS) alone (which leads to high IgM production), Blimp-1 is highly expressed, while cells co-stimulated with LPS and anti-mu F(ab')2 show low levels of Blimp-1 mRNA and no longer secrete Ig. I gamma 1 sterile transcripts are, however, up-regulated after receptor co-ligation. Addition of interleukin (IL)-2 and IL-5 to LPS + anti-mu F(ab')2-treated primary B cells led to up-regulation of Blimp-1 and IgM secretion. Transfection of a Blimp-1 expression vector also induced IgM secretion. The data indicate that Blimp-1 is an important regulator of immunoglobulin secretion by primary B cells, and suggest that its level of expression may determine the differentiation to Ig-secreting plasma cells or entrance and maintenance in the memory pool.
Schliephake
D E
DE
Institute for Virology and Immunobiology, University of Würzburg, Germany.
Schimpl
A
A
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D007133:Immunoglobulin Joining Region / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000096:biosynthesis; D012097:Repressor Proteins; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D007140:Immunoglobulin Fab Fragments; D007133:Immunoglobulin Joining Region; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D015848:Interleukin-5; D008070:Lipopolysaccharides; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D014157:Transcription Factors; C044203:anti-IgM; D000074462:Positive Regulatory Domain I-Binding Factor 1