Recombinant CD40 ligand stimulation of murine B cell growth and differentiation: cooperative effects of cytokines.
The ligand for the B cell surface antigen CD40 was recently cloned from a murine thymoma cDNA library and shown to be expressed on activated T cells. In this study, we investigate the biological effects of murine recombinant CD40 ligand. The recombinant CD40 ligand expressed on the CV-1/EBNA monkey fibroblast cell line directly activated resting B cell to express elevated levels of cell surface class II major histocompatibility complex and CD23 molecules. CD40 ligand also stimulated B cell proliferation, reaching maximal levels on day 2 of culture and declining thereafter. This effect was positively regulated by other cytokines, most notably interleukin (IL)-4 and IL-5. By itself, CD40 ligand had no effect upon immunoglobulin secretion by B cells. However, when B cells were treated with CD40 ligand plus cytokines, immunoglobulin secretion was stimulated in a cytokine-dependent and isotype-specific manner. IL-4 was a potent co-stimulator of IgE and IgG1 in the presence of CD40 ligand, and IL-5 acted synergistically with IL-4 in these responses as well as in IgM and IgG3 production. Taken together, the results indicate that CD40 ligand is a potent regulatory molecule for B cell growth and differentiation, and its activities are potentiated in a cytokine-specific manner.
Maliszewski
C R
CR
Department of Immunology, Immunex Research and Development Corporation, Seattle, WA 98101.
Grabstein
K
K
Fanslow
W C
WC
Armitage
R
R
Spriggs
M K
MK
Sato
T A
TA
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D023201:CD40 Ligand; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology
D000954:Antigens, Surface; D016207:Cytokines; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D023201:CD40 Ligand; D007073:Immunoglobulin E