The B-cell antigen receptor (BCR) is essential for B-cell selection, expansion, differentiation, and antigen presentation. The BCR is a multimeric complex consisting of membrane immunoglobulin (mIg) and the CD79a/b heterodimer, necessary for both surface expression and signal transduction. B-chronic lymphocytic leukemia (B-CLL) is characterized by low mIg expression and a reduced BCR signaling capacity. Different mechanisms have been proposed to explain this diminished receptor function, such as kinase-activation defects, reduced or absent expression of CD79b, and, most recently, expression of a truncated form of CD79b, ΔCD79b.
In this issue Cragg et al (page 3068) report that ΔCD79b is overexpressed in most B-CLL cases, as compared with peripheral blood B cells. They provide convincing evidence that overexpression of ΔCD79b is not associated with reduced mIg levels per se but (more importantly) inhibits BCR-induced apoptosis and that an intact immunoreceptor tyrosine-based activation motive is necessary for this inhibitory activity of ΔCD79b. Although these func- tional effects of ΔCD79b were demon- strated in a panel of ΔCD79b-transfected Burkitt cell lines and not in B-CLL cells, the study suggests that regulation of ΔCD79b expression could be an important mechanism controlling BCR signaling, possibly by sequestering critical signaling molecules away from the BCR. It is unresolved whether the relatively high expression in B-CLL is just a reflection of expression levels in their nonmalignant counterparts or whether up-regulation of the truncated molecule is a specific feature contributing to the malignant phenotype. In view of the recent finding of a BCR-signaling gene expression signature in CLL patients with (poor prognosis) unmutated IgVH genes, it would be very interesting to compare ΔCD79b expression levels in mutated CLL with those in unmutated CLL. These studies might increase our insight into the pathophysiology of CLL.
