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) 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 delta-chain antibodies (Gadelta-ab) caused [Ca(++)]i mobilization and tyrosine kinase phosphorylation in a manner not different from that observed after goat antihuman mu-chain antibody (Gamu-ab) treatment in vitro. However, Gadelta-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 Gadelta-ab did not prevent apoptosis of B-CLL cells induced by Gamu-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. (Blood. 2000;95:1199-1206)
Zupo
S
S
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy. szupo@hp380.ist.unige.it
Massara
R
R
Dono
M
M
Rossi
E
E
Malavasi
F
F
Cosulich
M E
ME
Ferrarini
M
M
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000097:blood; D000943:Antigens, Differentiation / Q000097:blood*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D002118:Calcium / Q000097:blood; D002453:Cell Cycle; D002454:Cell Differentiation; D003432:Cross-Linking Reagents; D005434:Flow Cytometry; D006801:Humans; D007072:Immunoglobulin D / Q000097:blood*; D007075:Immunoglobulin M / Q000097:blood*; D007142:Immunoglobulin gamma-Chains / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000097:blood*; D009336:Necrosis; D019000:Phosphotyrosine / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000906:Antibodies; D015703:Antigens, CD; D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007142:Immunoglobulin gamma-Chains; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D019000:Phosphotyrosine; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium