Induction of human IgE synthesis by CD4+ T cell clones. Requirement for interleukin 4 and low molecular weight B cell growth factor.
We have analyzed in detail the precise requirements for the induction of human IgE synthesis using several experimental approaches with purified B cells and well-characterized alloantigen-specific CD4+ T cell clones expressing different profiles of lymphokine secretion. Using these clones under cognate conditions in which the B cells expressed alloantigens recognized by the cloned T cells, we have confirmed that IL-4 is required for the induction of IgE synthesis, but we have clearly demonstrated that IL-4 by itself is not sufficient. With several cloned CD4+ T cell lines, including an IL-4-producing clone that could not induce IgE synthesis, and cloned T cells pretreated with cyclosporin A to inhibit lymphokine synthesis, we showed that Th cell-B cell interactions are necessary for IgE synthesis, and that low molecular weight B cell growth factor (LMW-BCGF) and IL-4, in combination, are lymphokines of major importance in the induction of IgE synthesis. Together our results indicate that optimal induction of an IgE-specific response requires the exposure of B cells to a particular complex of signals that include (a) a signal(s) involving Th-B cell interaction that primes B cells to receive additional signals from soluble lymphokines, (b) a specific B cell proliferative signal provided by LMW-BCGF, and (c) a specific B cell differentiation signal provided by IL-4.
DeKruyff
R H
RH
Department of Pediatrics, Stanford University School of Medicine, California 94305.
Turner
T
T
Abrams
J S
JS
Palladino
M A
MA
Umetsu
D T
DT
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003524:Cyclosporins / Q000494:pharmacology; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015847:Interleukin-4 / Q000502:physiology*; D008211:Lymphocyte Cooperation; D008970:Molecular Weight; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D003524:Cyclosporins; D007376:Interleukin-2; D015847:Interleukin-4; D007073:Immunoglobulin E