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Blood, 1 November 2002, Vol. 100, No. 9, pp. 3068-3076
PLENARY PAPER
The alternative transcript of CD79b is overexpressed in
B-CLL and inhibits signaling for apoptosis
Mark S. Cragg,
H. T. Claude Chan,
Mathew D. Fox,
Alison Tutt,
Aimée Smith,
David G. Oscier,
Terry J. Hamblin, and
Martin J. Glennie
From the Tenovus Research Laboratory, Cancer Sciences
Division, School of Medicine, University of Southampton, United
Kingdom; and the Department of Haematology, Royal Bournemouth Hospital,
Bournemouth, United Kingdom.
The B-cell receptor (BCR) for antigen is composed of surface
immunoglobulin (sIg), which provides antigen specificity, and a
noncovalently associated signaling unit, the CD79a/b heterodimer. Defects in CD79 can influence both BCR expression and signaling and may
explain why cells from certain malignancies, such as
B-chronic lymphocytic leukemia (B-CLL), often express
diminished and inactive BCR. Recently, an alternative transcript of
CD79b ( CD79b) has been reported that is up-regulated in B-CLL and
may explain this diminished BCR expression. Here we assess the
expression of CD79b in B-CLL and other lymphoid malignancies and
investigate its function. High relative expression of CD79b was
confirmed in most cases of B-CLL and found in 6 of 6 cases of splenic
lymphomas with villous lymphocytes (SLVLs) and hairy cell leukemia. In
a range of Burkitt lymphoma cell lines, expression of CD79b was
relatively low but correlated inversely with the ability of the BCR to
signal apoptosis when cross-linked by antibody (Ab).
Interestingly, when Ramos-EHRB cells, which express low CD79b, were
transfected with this transcript, they were transformed from being
sensitive to anti-Fcµ-induced apoptosis to being highly resistant.
Although CD79b was expressed as protein, its overexpression did not
reduce the level of cell surface BCR. Finally, we showed that the
inhibitory activity of CD79b depended on an intact leader sequence
to ensure endoplasmic reticulum (ER) trafficking and a
functional signaling immunoreceptor tyrosine-based activation
motif (ITAM) in its cytoplasmic tail. These results point to
CD79b being a powerful modulator of BCR signaling that may play an
important role in normal and malignant B cells.
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