CD38 expression distinguishes two groups of B-cell chronic lymphocytic leukemias with different responses to anti-IgM antibodies and propensity to apoptosis.
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.
Zupo
S
S
Servizio di Immunologia Clinica, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Isnardi
L
L
Megna
M
M
Massara
R
R
Malavasi
F
F
Dono
M
M
Cosulich
E
E
Ferrarini
M
M
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000166:cytology*; D014408:Biomarkers, Tumor; D002118:Calcium / Q000502:physiology; D002453:Cell Cycle; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D015847:Interleukin-4 / Q000502:physiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000502:physiology*; D011940:Receptor Aggregation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D002118:Calcium