Engagement of CD14 on monocytes inhibits the synthesis of human Igs, including IgE.
Engagement of CD14 on normal human monocytes results in monocyte activation and, furthermore, delivers a negative signal that terminates T cell proliferation. We show herein that engagement of selected CD14 epitopes by specific mAbs inhibited PWM-induced IgM and IgG synthesis, as well as IL-4-dependent IgE synthesis by human PBMCs. Inhibition by anti-CD14 mAb was still evident when the Ab was added after 6 days of culture, suggesting that inhibition targets a late B cell activation event. In experiments that focused on the role of CD14 in IgE regulation, suppression of IgE synthesis after CD14 engagement did not result from the release of inhibitory monokines (IL-10, TGF-beta, and PG). In fact, neutralizing Abs and specific inhibitors did not restore the IgE response and anti-CD14-conditioned monocyte supernatants did not inhibit IgE synthesis. On the other hand, inhibition of IgE synthesis by anti-CD14 mAb was not likely to be caused by the lack of soluble factors with amplificatory effects on the IgE response, because addition of either rIL-6 or rTNF-alpha did not overcome CD14-dependent inhibition of IgE production. IgE inhibition after CD14 engagement was exerted at the B cell level, inasmuch as it was observed not only in T cell-dependent IgE induction i.e., mononuclear cells stimulated with IL-4, but also in T cell-independent systems, i.e., T cell-depleted populations stimulated with IL-4 plus anti-CD40 mAb or IL-4 plus hydrocortisone. These data indicate that CD14 plays a regulatory role in B cell responses.
Jabara
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Division of Immunology, Children's Hospital, Boston, MA 02115.
Vercelli
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D000917:Antibody Formation; D015703:Antigens, CD / Q000276:immunology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D000955:Antigens, T-Independent / Q000276:immunology; D002478:Cells, Cultured; D000939:Epitopes; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000502:physiology*; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000955:Antigens, T-Independent; D000939:Epitopes; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E