Immunomodulatory role of IL-4 on the secretion of Ig by human B cells.
The effect of IL-4 on the production of Ig by human B cells was examined. Highly purified B cells were stimulated with Staphylococcus aureus (SA) and IL-4 alone or in combination with various other cytokines and the supernatants assayed for Ig by isotype-specific ELISA. IL-4 (10 to 100 U/ml) did not support Ig secretion by SA-stimulated blood, spleen, or lymph node B cells, whereas IL-2 supported the production of all isotypes including IgE. Moreover, IL-4 suppressed the production of all isotypes of Ig by B cells stimulated with SA and IL-2 including IgG1, IgG2, and IgE. IL-4-mediated suppression was partially reversed by IFN-gamma or -alpha and low m.w. B cell growth factor. TNF-alpha and IL-6 did not reverse the IL-4-induced suppression of Ig production. The inhibitory action of IL-4 on Ig production appeared to depend on the polyclonal activator used to stimulate the B cells. Thus, Ig secretion by B cells activated by LPS and supported by IL-2 was not inhibited by IL-4. Whereas IL-4 alone supported minimal Ig production by LPS-activated B cells, it augmented production of all Ig isotypes in cultures stimulated with LPS and supported by IL-2. IFN-gamma further enhanced production of Ig in these cultures. When the effect of IL-4 on the responsiveness of B cells preactivated with SA and IL-2 was examined, it was found not to inhibit but rather to promote Ig production modestly. A direct effect of IL-4 on the terminal differentiation of B cells was demonstrated using B lymphoblastoid cell lines. IL-4 was able to enhance the Ig secreted by an IgA-secreting hybridoma, 219 and by SKW6-CL-4, an IL-6-responsive IgM-secreting EBV transformed B cell line. These results indicate that IL-4 exerts a number of immunoregulatory actions on human B cell differentiation. It interferes with the activation of B cells by SA and IL-2, but promotes the differentiation of preactivated B cells, B cell lines, and B cells activated by LPS without apparent isotype specificity.
Splawski
J B
JB
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Jelinek
D F
DF
Lipsky
P E
PE
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000328:Adult; D001402:B-Lymphocytes / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis*; D007166:Immunosuppressive Agents / Q000502:physiology; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2; D015847:Interleukin-4; D007378:Interleukins / Q000502:physiology*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000187:drug effects; D013211:Staphylococcus aureus
D000276:Adjuvants, Immunologic; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D007370:Interferon Type I; D007376:Interleukin-2; D007378:Interleukins; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007371:Interferon-gamma