Transforming growth factor-beta (TGF beta) inhibition of Epstein-Barr virus (EBV)- and interleukin-4 (IL-4)-induced immunoglobulin production in human B lymphocytes.
This study reports on the effects of TGF beta on the secretion of Ig isotypes by highly purified (> 99% CD20-positive) human peripheral blood B cells. Stimulation of these B cell preparations with EBV resulted in the secretion of IgM, IgG, and IgA and the addition of IL-4 induced readily detectable levels (> 100 ng/ml) of IgE between 10 and 25 days of culture. TGF beta 1 and TGF beta 2 showed similar dose-dependent suppression of IgM, IgG, and IgA, and the relative proportion of IgG and IgA remained unchanged in the presence of TGF beta. IgE production induced by EBV and IL-4 was significantly inhibited by TGF beta. TGF beta effects on Ig secretion were not related to inhibition of B cell proliferation by this cytokine. In contrast to these TGF beta effects on EBV activation of primary B cells, the constitutive Ig secretion by EBV-transformed B cells was resistant to TGF beta, while the increase in Ig secretion induced by IL-6 was inhibited by TGF beta. Thus, TGF beta inhibits the EBV-induced secretion of the major Ig isotypes in peripheral blood B cells and has differential effects on Ig secretion by transformed B cells.
Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla 92093.
K P
KP
Machold
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DA
Carson
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Lotz
D001402:B-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007165:Immunosuppression Therapy; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology*
D007132:Immunoglobulin Isotypes; D007136:Immunoglobulins; D016212:Transforming Growth Factor beta; D015847:Interleukin-4