Interleukin 4 inhibits in vitro proliferation of leukemic and normal human B cell precursors.
In the present study, we have investigated the effects of IL-4 on the proliferation and differentiation of leukemic and normal human B cell precursors (BCP). We have demonstrated that IL-4 significantly inhibited spontaneous [3H]thymidine ([3H]-TdR) incorporation by leukemic blasts from some B lineage acute lymphoblastic leukemia (BCP-ALL) patients (8 of 14). Furthermore, IL-4 was found to suppress the spontaneous and factor-dependent (IL-7 and IL-3) proliferation of normal BCP (CD10+ surface [s] IgM- cells) isolated from fetal bone marrow. Maximum growth inhibition of either leukemic or normal BCP was reached at low IL-4 concentrations (10 U/ml), and the effect was specifically neutralized by anti-IL-4 antibody. IL-4 was further found to induce the expression of CD20 antigen on BCP-ALL cells from a number of the cases examined (5 of 8), but in contrast to leukemic cells, IL-4 failed to induce CD20 antigen on normal BCP. Finally, IL-4 was found to induce neither the expression of cytoplasmic mu chain, nor the appearance of sIgM+ cells in cultures of normal or leukemic BCP. Our data indicate that IL-4 has the potential to inhibit cell proliferation in leukemic and normal human B lymphopoiesis but is unable to drive the transition from BCP to mature B cells.
Pandrau
D
D
Laboratory for Immunological Research, Schering-Plough, Dardilly, France.
Saeland
S
S
Duvert
V
V
Durand
I
I
Manel
A M
AM
Zabot
M T
MT
Philippe
N
N
Banchereau
J
J
D015703:Antigens, CD / Q000032:analysis; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002051:Burkitt Lymphoma / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007075:Immunoglobulin M / Q000032:analysis; D015847:Interleukin-4 / Q000494:pharmacology*; D015260:Neprilysin / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D007075:Immunoglobulin M; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D015260:Neprilysin