A transforming growth factor-beta regulable RNA-binding protein interacts specifically with germline Ig alpha transcripts.
Isotype switching is presaged by the transcriptional activation of the heavy chain class gene (CH) to which recombination will occur. As a result, mRNA or germline transcripts from the unrearranged gene accumulate in the cytoplasm. Previous studies demonstrated that transforming growth factor (TGF)-beta stimulated isotype switching to IgA in cultures of lipopolysaccharide (LPS)-stimulated murine B cells and increased the stability of C alpha mRNAs. The present study demonstrates that LPS-stimulated B cells express a 45 kDa protein, I alpha BP, that specifically binds to germline alpha transcripts. Following addition of TGF-beta, the binding activity of this protein is significantly reduced. The identification of a cytokine regulable RNA-binding protein that interacts with germline transcripts supports the idea that these transcripts are involved in recombination and raises the possibility that RNA-protein interactions play a role in regulating isotype switching.
Edmiston
J S
JS
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond 23298, USA.
Lebman
D A
DA
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002478:Cells, Cultured; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000235:genetics*; D017578:Immunoglobulin Class Switching; D007137:Immunoglobulin alpha-Chains / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000302:isolation & purification* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology*
D007070:Immunoglobulin A; D007137:Immunoglobulin alpha-Chains; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D016212:Transforming Growth Factor beta