B cell differentiation and interleukin 2 (IL2): corticosteroids interact with monocytes to enhance the effect of IL2.
Upon in vitro activation by Staphylococcus aureus Cowan I strain (SAC) human peripheral blood B cells produce only marginal amounts of Ig when cultured in the presence of interleukin 2 (IL2; 10 U/ml). This response is only moderately increased by the addition of monocytes or of IL1. In the presence of dexamethasone (DM; 10(-7)-10(-8) M) microgram amounts of both IgM and IgG are produced in co-cultures of B cells and monocytes. This response is not modified by inhibitors of cyclooxygenase and is specifically inhibited by a monoclonal antibody interfering with the binding of IL2 to its receptor. This enhancing effect of DM is not observed in the absence of monocytes even if IL1 is added to the cultures. Moreover, monocytes pretreated with DM stimulate the response of B cells cultures in the absence of DM. Enhancement of Ig production by DM and monocytes could be demonstrated with B cells obtained from a patient suffering from a hyperlymphocytic form of B cell type chronic lymphocytic leukemia, and in this case only IgM was produced. Importantly, DM fully inhibited the IL2-dependent proliferation of these monoclonal B cells. Thus, physiological concentrations of DM can modulate monocytic function to enhance the differentiative effect of IL2.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000648:ultrastructure; D002450:Cell Communication / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007376:Interleukin-2 / Q000494:pharmacology*; D007945:Leukemia, Lymphoid / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000276:immunology / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D015375:Receptors, Interleukin-2
D000305:Adrenal Cortex Hormones; D007074:Immunoglobulin G; D007376:Interleukin-2; D011965:Receptors, Glucocorticoid; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; C028697:dexamethasone receptor; D003907:Dexamethasone