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CD38 expression distinguishes two groups of B-cell chronic lymphocytic
leukemias with different responses to anti-IgM antibodies and propensity to
apoptosis
S Zupo, L Isnardi, M Megna, R Massara, F Malavasi, M Dono, E Cosulich and M Ferrarini
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul
Cancro, Genova, Italy.
The expression of CD38 by B cells chronic lymphocytic leukemia (B-CLL) was
studied in 20 untreated patients. The cells expressed abundant CD38
(relative fluorescence intensity range, 6 to 15) in 6 cases (group I
patients), whereas CD38 expression was low to absent (relative fluorescence
intensity range, 0 to 3) in the remaining cases (group II patients).
Exposure of the cells from group I patients to goat antihuman mu chain
antibodies (Ga mu-ab) resulted in the elevation of intracellular free Ca2+
concentration([Ca2+]i) followed by apoptosis. In contrast, exposure of
group II cells to Ga mu-ab was not followed by increased levels of [Ca2+]i,
programmed cell death or cell proliferation. No differences in the
expression of surface IgM were noted in the two groups of B-CLL cells.
Normal peripheral blood B cells, which expressed low to absent CD38, were
capable of mobilizing [Ca2+]i and of proliferating after exposure to Ga
mu-ab. The collected data suggest that, although group I B-CLL cells were
able to transduce the signals delivered by IgM crosslinking, this pathway
was severely impaired in group II B-CLL cells. However, unlike that
observed in normal circulating B cells, stimulation of group I cells with
Ga mu-ab resulted in apoptosis rather than proliferation. CD38 did not
appear to be directly involved in [Ca2+]i mobilization induced by Ga mu-ab
in group I B-CLL cells because their exposure to anti-CD38 monoclonal
antibodies failed to cause [Ca2+]i mobilization or to block the [Ca2+]i
response induced by Ga mu-ab. These data indicate that CD38 expression
identified a particular subset of B-CLL cells with defined functional
properties, including the propensity to undergo apoptosis.
Volume 88,
Issue 4,
pp. 1365-1374,
08/15/1996
Copyright © 1996 by The American Society of Hematology
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