Different isoforms of BSAP regulate expression of AID in normal and chronic lymphocytic leukemia B cells

ABSTRACT

Activation-induced cytidine deaminase (AID) is key to initiating somatic hypermutation (SHM) and class switch recombination (CSR), but its mode of action and regulation remains unclear. Since Pax-5 and Id-2 transcription factior play an opposing role in AID regulation, we have studied the expression of Pax-5, Id-2, and prdm-1 genes in 54 chronic lymphocytic leukaemia (CLL) B cells. In 21 cases, presence of AID is constantly associated with high expression of the complete form of the Pax-5-gene (Pax-5a) and lower expression of the Id-2 and prdm-1 transcripts. In 33 cases, the abscence of AID expression and CSR is associated with a reduction of Pax-5a and the appearance of a spliced form with a deletion in exon 8 (Pax-5/AEx8). Stimulation with CD40L+Interleukin 4 (IL-4) induces CSR, the presence of AID transcripts, up-regulation of Pax-5a and down-regulation of Pax-5/A-Ex8, and Id-2 and prdm-1 transcripts. Pax-5a and Pax-5/A-Ex8 are translated into 2 isoforms of the B-cell specific activator protein (BSAP) and both are able to bind the AID-promoter region. Overall, there results suggests that Pax-5/A-Ex8 could play an important role in the control of its own transcription and indirectly in AID expression and CSR