Cytokine-induced proliferation and immunoglobulin production of human B lymphocytes triggered through their CD40 antigen.
Human resting B lymphocytes enter a state of sustained proliferation when incubated with both mouse fibroblastic L cells stably expressing Fc gamma RII/CDw32 and anti-CD40 antibodies. We have explored the effects of 11 recombinant human cytokines (CKs) on induced cell proliferation and immunoglobulin (Ig) production. Interleukin 4 (IL-4) was the only CK able to enhance anti-CD40-induced B cell multiplication as measured by enumeration of viable cells, and interferon gamma (IFN-gamma) further stimulated this induced proliferation. IL-4 enhanced the production of IgM and IgG by B cells and induced them to produce IgE. Combinations of IL-4 and IL-2 resulted in the production of large amounts of IgM and IgA. Interestingly, IFN-gamma did not inhibit the production of IgE by cells stimulated with anti-CD40 and IL-4. None of the tested CK combinations resulted in the production of large quantities of IgG. Therefore, this new culture system represents a unique model to study isotype regulation in highly purified human B lymphocytes, in addition to allowing the generation of long-term factor-dependent human B cell lines.
Rousset
F
F
Laboratory for Immunological Research, Schering-Plough, Dardily, France.
Garcia
E
E
Banchereau
J
J
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D019013:CD40 Antigens; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015848:Interleukin-5 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D014066:Palatine Tonsil / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2; D015848:Interleukin-5; D015850:Interleukin-6; D011994:Recombinant Proteins; D007371:Interferon-gamma