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.