Apoptosis or plasma cell differentiation of CD38-positive B-chronic lymphocytic leukemia cells induced by cross-linking of surface IgM or IgD

Previously, we demonstrated that B-chronic lymphocytic leukemia (B-CLL) cel ls could be divided into 2 groups depending on the expression of CD38 by th e malignant cells. The 2 groups differed in their signal-transducing capaci ties initiated by cross-linking of surface IgM;; only in CD38-positive cell s was an efficient signal delivered, invariably resulting in cell apoptosis , In this study, we investigated the effect of surface IgD cross-linking in 10 patients with CD38-positive B-CLL. Exposure of the malignant cells to g oat antihuman delta-chain antibodies (Ga delta-ab) caused [Ca++]i mobilizat ion and tyrosine kinase phosphorylation in a manner not different from that observed after goat antihuman mu-chain antibody (Ga mu-ab) treatment in vi tro. However, Ga delta-ab-treated cells failed to undergo apoptosis and ins tead displayed prolonged survival in culture and differentiated into plasma cells when rlL2 was concomitantly present. Cross-linking of surface IgD fa iled to induce proliferation of the malignant cells in vitro. Moreover, tre atment with Ga delta-ab did not prevent apoptosis of B-CLL cells induced by Ga mu-ab. Collectively, these experiments demonstrated that IgM and IgD ex pressed by the same cell may deliver opposite signals under particular circ umstances and provide some clues for the understanding of the pathophysiolo gy of B-CLL.(Blood. 2000;95:1199-1206) (C) 2000 by The American Society of Hematology.