Modulation of human IgE synthesis by transforming growth factor-beta.
Exogenous transforming growth factor-beta 2 (TGF-beta 2) markedly inhibits the interleukin 4 (IL4)-stimulated synthesis of human IgE in three models where the B cell co-stimulation signals are contact dependent. This concerns T cell-dependent IgE production by (i) unfractionated peripheral blood mononuclear cells (PMBC) cultured with IL4 and (ii) highly purified B cells cocultured with irradiated EL4 thymoma cells in the presence of IL4 and phorbol myristate acetate, as well as monocyte-dependent IgE production by rigorously T cell-depleted PBMC cultured with IL4 and hydrocortisone. The suppression is not isotype specific. TGF-beta exerts its effect by inhibiting the proliferation of B cells and perhaps also the differentiation of proliferating B cells. However, at a later stage of differentiation, IgE B cells are refractory to the inhibitory effect of TGF-beta, as shown by the slight but significant increase of the spontaneous secretion of IgE by PBMC of atopic patients. This enhancement is due to the suppression of endogenous interferon-gamma production. Most interestingly the synthesis of IgE by highly purified B cells costimulated with IL4 and Epstein-Barr virus is unaffected by TGF-beta. It is concluded that TGF-beta mainly acts by inhibiting IL4-supported B cell proliferation; however, its effects depend upon the B cell costimulation signals that are required together with IL4 for the induction of IgE synthesis.
Wu
C Y
CY
University of Montreal, Notre-Dame Hospital, Quebec, Canada.
Brinkmann
V
V
Cox
D
D
Heusser
C
C
Delespesse
G
G
D000921:Antibody-Producing Cells / Q000166:cytology; D001402:B-Lymphocytes / Q000166:cytology / Q000382:microbiology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood; D007108:Immune Tolerance / Q000187:drug effects; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000187:drug effects; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008214:Lymphocytes / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007073:Immunoglobulin E