title: Inhibitory influence of IL-4 on human B cell responsiveness.
abstract: The role of IL-4 in human B cell activation, proliferation, and differentiation was examined. rIL-2, but not rIL-4, was able to promote maximum proliferation and generation of Ig-secreting cells in cultures of highly purified B cells stimulated with Cowan I Staphylococcus aureus (SA). Addition of rIL-4 to rIL-2-supported cultures of SA-stimulated peripheral blood, spleen, or lymph node B cells dramatically suppressed both proliferation and differentiation. Results from experiments in which rIL-4 was added to culture at progressively later times indicated a requirement for rIL-4 to be present during the first 2 days of a 5-day incubation to cause inhibition of responsiveness. When a two-stage culture system was utilized, rIL-4 was found to support proliferation or differentiation of B cells initially activated with SA for 2 days only minimally. However, rIL-4 did not inhibit responses of SA preactivated B cells supported by IL-2. The presence of rIL-4 during the initial 48-h activation of B cells with SA and rIL-2 resulted in a profound inhibition of the ability of the activated B cells to respond subsequently to rIL-2 or lymphokine-rich T cell supernatants. A similar 48-h incubation with rIL-4 alone without SA had no effect on subsequent B cell responsiveness. The presence of rIFN-gamma during B cell activation decreased the inhibitory effect of IL-4. Other cytokines including IFN-alpha, IL-1, and commercially available low m.w. B cell growth factor also diminished the inhibitory effect of IL-4. These results indicate that IL-4 inhibits the capacity of human B cells to be activated maximally by SA and rIL-2 and therefore suggest a new immunomodulatory role for this cytokine.
authors.affiliation: Harold C. Simmons Arthritis Research Center, Dallas, TX 75235.
authors.forename: D F
authors.initials: DF
authors.lastname: Jelinek
authors.forename: P E
authors.initials: PE
authors.lastname: Lipsky
mesh_terms: D000954:Antigens, Surface / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001688:Biological Products / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013209:Staphylococcal Vaccines / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D000954:Antigens, Surface; D001688:Biological Products; D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007378:Interleukins; D011994:Recombinant Proteins; D013209:Staphylococcal Vaccines; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA