CD38 expression distinguishes two groups of B-cell chronic lymphocytic leukemias with different responses to anti-IgM antibodies and propensity to apoptosis

Abstract

The expression of CD38 by B cells of 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 μ chain antibodies (Gaμ-ab) resulted in the elevation of intracellular free Ca2+ concentration ([Ca2+](i)) followed by apoptosis. In contrast, exposure of group II cells to Gaμ-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 Gaμ- ab. The collected data suggest that, although group I B-CLL cells were able to transduce the signals delivered by IgM cross-linking, this pathway was severely impaired in group II B-CLL cells. However, unlike that observed in normal circulating g cells, stimulation of group I cells with Gaμ-ab resulted in apoptosis rather than proliferation. CD38 did not appear to be directly involved in [Ca2+](i) mobilization induced by Gaμ-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 Gaμ-ab. These data indicate that CD38 expression identifies a particular subset of B-CLL cells with defined functional properties, including the propensity to undergo apoptosis.