The role of BSAP in immunoglobulin isotype switching and B-cell proliferation.

Abstract

A role for the transcription factor B cell-specific activator protein (BSAP) in switch recombination has been proposed because binding sites for this protein have been found near switch regions of several isotypes. We have attempted to assess BSAP's role by altering the expression of this protein in B cells switching in culture to IgG1. We found that a phosphorothioate oligonucleotide antisense to the BSAP translation initiation site was able, when incubated with B cells, to decrease BSAP activity in nuclear extracts, and that IgG1 expression was reduced in such cells compared to cells incubated with control oligonucleotides. However, it is not clear whether this apparent reduction in switch recombination was mediated by the known BSAP binding sites in the immunoglobulin heavy chain locus because the antisense experiments revealed an additional activity of this protein: it is a rate-limiting regulator of cell proliferation. Down-regulation of BSAP was associated with decreased proliferation, while increasing BSAP (by transfection with a BSAP expression plasmid) increased proliferation. Thus because switch recombination apparently requires cell division, the effect of BSAP down-regulation on switching might have resulted from decreased proliferation. The role of BSAP in B cell proliferation suggests that dysregulation of this protein could contribute to neoplastic transformation of B cells. Because of BSAP's many activities, experiments to elucidate the mechanisms of its effects on switching and proliferation will be challenging.