Blood, 1 November 2002, Vol. 100, No. 9, pp. 3061-3062
Curtailing BCR signaling
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, 
CD79b.
In this issue Cragg et al (page 3068) report that CD79b is
overexpressed in most B-CLL cases, as compared with peripheral blood B cells. They provide convincing evidence that overexpression of
CD79b 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 CD79b. Although these func- tional
effects of CD79b were demon- strated in a panel of
CD79b-transfected Burkitt cell lines and not in B-CLL cells, the
study suggests that regulation of CD79b 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 CD79b expression levels in mutated CLL with those in
unmutated CLL. These studies might increase our insight into
the pathophysiology of CLL.
René A. W. van Lier and Marinus
J. H. van Oers
Amsterdam Academic Medical Center
