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Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1199-1206
Apoptosis or plasma cell differentiation of
CD38-positive B-chronic lymphocytic leukemia cells induced by
cross-linking of surface IgM or IgD
Simona Zupo,
Rosanna Massara,
Mariella Dono,
Edoardo Rossi,
Fabio Malavasi,
M. Elisabetta Cosulich, and
Manlio Ferrarini
From Servizio di Immunologia Clinica, Istituto Nazionale per la
Ricerca sul Cancro; Dipartimento di Oncologia, Biologia e Genetica,
Università degli Studi di Genova; Unità Anticorpi
Monoclonali, Advanced Biotechnology Center, Genoa, Italy; and Instituto
Biologia e Genetica, Università di Amcona, Italy.
Previously, we demonstrated that B-chronic lymphocytic leukemia
(B-CLL) cells could be divided into 2 groups depending on the
expression of CD38 by the malignant cells. The 2 groups differed in
their signal-transducing capacities initiated by cross-linking of
surface IgM; only in CD38-positive cells 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 goat
antihuman  -chain antibodies (Ga-ab) caused
[Ca++]i mobilization and tyrosine kinase
phosphorylation in a manner not different from that observed after goat
antihuman µ-chain antibody (Gaµ-ab) treatment in vitro. However,
Ga-ab-treated cells failed to undergo apoptosis and instead
displayed prolonged survival in culture and differentiated into plasma
cells when rIL2 was concomitantly present. Cross-linking of surface IgD
failed to induce proliferation of the malignant cells in vitro.
Moreover, treatment with Ga-ab did not prevent apoptosis of B-CLL
cells induced by Gaµ-ab. Collectively, these experiments demonstrated that IgM and IgD expressed by the same cell may deliver opposite signals under particular circumstances and provide some clues for the
understanding of the pathophysiology of B-CLL.
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