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Growth- and differentiation-associated expression of bcl-2 in B-chronic
lymphocytic leukemia cells
M Schena, LG Larsson, D Gottardi, G Gaidano, M Carlsson, K Nilsson and F Caligaris- Cappio
Dipartimento di Scienze Biomediche e Oncologia Umana, Universita di Torino,
Italy.
The bcl-2 gene is translocated into the Ig loci in about 80% of human
follicular lymphomas and in 10% of B-type chronic lymphocytic leukemias
(B-CLL), resulting in a high level of expression. We have compared the
expression of bcl-2 transcripts and protein in B-CLL cells in their normal
equivalent CD5+ B cells and in normal B-cell populations representative of
different in vivo and in vitro stages of activation and proliferation. We
report here that bcl-2 was expressed in 11 of 11 cases of CD5+ B-CLL
clones, contrasting with the absent expression in normal CD5+ B cells.
Activation of 173 and 183 B-CLL cells by phorbol esters
(12-O-tetradecanoylphorbol-13-acetate [TPA]) to IgM secretion without
concomitant DNA synthesis resulted in a rapid but transient downregulation
of bcl-2 expression. In contrast, the reduction of bcl-2 at both the
messenger RNA and protein levels was sustained after mitogenic stimulation,
suggesting that bcl-2 expression and proliferation are inversely related in
these cells. This notion was further supported by immunocytochemical
analysis showing that bcl-2 was primarily expressed in small resting
lymphocytes and in cells differentiating to the plasma cell stage, but less
expressed in Ki67- positive proliferating B blasts. Moreover, it was also
supported by the low level of bcl-2 in exponentially growing Epstein-Barr
virus-carrying lymphoblastoid and B-CLL cell lines. The regulation of bcl-2
expression in B-CLL resembled that of normal tonsillar follicular B cells,
in which a high level of expression was found in resting mantle zone B
cells but not in the proliferating germinal center B cells. Based on these
findings and the role of bcl-2 in maintaining B-cell memory, we propose
that the phenotype of B-CLL cells corresponds to a mantle zone memory-type
B cell.
Volume 79,
Issue 11,
pp. 2981-2989,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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