IL-4 induces loss of B lymphocyte Fc gamma R II ligand binding capacity.
Murine B lymphocytes cultured for 24 h with rIL-4 lost (mean reduction of 88%, range 81 to 96%) the capacity to bind Ag-IgG antibody complexes to B lymphocytes as assessed by flow microfluorometry. This effect was specific in that it was not seen with IL-1, IL-2, or IFN-gamma; IL-4 did not have a similar effect on other B lymphocyte membrane molecules; and the effect was completely prevented by anti-IL-4 (mAb 11B11). More than 60% inhibition of the binding of complexes was seen with as little as 1 U/ml of IL-4 although maximal inhibition was seen with greater than or equal to 30 U/ml. IL-4-induced inhibition of the binding of complexes was time dependent (the effect was first seen after 8 h and was not maximal until 24 h), temperature dependent (it did not occur at 4 degrees C), and reversible (B lymphocytes that had lost the ability to bind complexes due to IL-4 regained this capacity when re-cultured for 24 h in the absence of IL-4). The effect could be partially prevented by IFN-gamma. The inability to bind complexes appeared to be mainly due to an alteration of Fc gamma R (Fc Receptors) II rather than down-regulation of receptor expression because IL-4 induced only a moderate reduction in the binding of two Fc gamma R II specific mAb (20% for 2.4G2 and 32% for K9.361). The IL-4-induced loss of binding of complexes to B lymphocyte Fc gamma R II appears to be a novel form of receptor regulation (function rather than expression), and likely plays a role in the up-regulation of B lymphocytes by IL-4 by preventing Fc gamma R II-mediated inhibition of B lymphocyte responses.
Laszlo
G
G
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892.
Dickler
H B
HB
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice; D008811:Mice, Inbred DBA; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG; D013696:Temperature; D013997:Time Factors
D000936:Antigen-Antibody Complex; D000943:Antigens, Differentiation; D007166:Immunosuppressive Agents; D007378:Interleukins; D011961:Receptors, Fc; D017452:Receptors, IgG; D015847:Interleukin-4; D007371:Interferon-gamma