B-cell-specific activator protein (BSAP) is a recently identified member of the Pax-gene family of transcription factors; in the lymphoid system, BSAP is produced only in B cells. Here, Markus Neurath, Eckhard Stiiber and Warren Strober describe the molecular structure of BSAP and focus on the ability of this protein to regulate the expression of B-cell-specific genes. They propose that BSAP is a key protein of B cells and that it not only influences B-cell development, but also influences the balance between B-cell proliferation and immunoglobulin secretion at later stages of B-cell differentiation.

Regulation of the expression of individual B-cell-specific genes by nuclear trans-acting factors is now recognized as a central process that determines B-cell development and differentiation 1. In addition to Oct-2, NF-KB, PU. 1 and EBF (B-Lyf), this list must now include the B-cellspecific activator protein (BSAP) 2. BSAP was originally discovered by Barberis et al. 2, who showed it to be a mammalian homolog of the sea urchin tissue-specific activator protein (TSAP). TSAP interacts with the promoters of two non-allelic pairs of late histone genes and is a member of a class of transcription factors that bind DNA as a monomer. The 52 kDa BSAP protein was found to be encoded by the Pax5 gene and is thus a member of the highly conserved Pax-gene family of transcription factors 3. The Pax5 gene was recently mapped to chromosome 4 in mice and 9p13 in humans 4. Nuclear trans-acting factors of the Pax-gene family share a highly homologous region known as the'paired domain'(Fig. 1). This domain comprises two subdomains that bind to the two half-sites of a degenerate nonpalindromic consensus sequence in adjacent major grooves on the same side of the DNA helix s. Whereas the bipartite paired domain is both necessary and sufficient for DNA-binding activity, the trans-activation function of BSAP is located in the C-terminal Ser/Thr/Pro-rich region 6. Interestingly, a repressor