Differential regulation of murine B cell Fc gamma RII expression by CD4+ T helper subsets.
The murine B cell FcR for IgG (Fc gamma RII) is a membrane glycoprotein reported to mediate inhibition of B cell activation and differentiation. We show that IL-4 inhibits the enhanced expression of Fc gamma RII by LPS-stimulated B cells. This activity is completely reversed by anti-IL-4 mAb and is specific, in that multiple other lymphokines tested do not exert a similar effect. This effect of IL-4 is apparent by day 1 of culture, although maximal inhibition occurs on day 4 at a concentration of 500 U/ml. The IL-4-induced inhibition of enhanced Fc gamma RII expression by LPS stimulation observed on day 4 of culture is associated with a significant reduction in the steady state level of Fc gamma RII beta gene-specific mRNA. IFN-gamma which inhibits many of the effects of IL-4 on B cells, does not reverse the IL-4-induced inhibition of Fc gamma RII membrane expression nor the levels of beta gene-specific mRNA. Fc gamma RII expression is significantly increased in B cells stimulated with antigen-specific, CD4+ T cell clones of the Th1 type (i.e., IL-2 and IFN-gamma-producing). By contrast, three different Th2 clones (i.e., IL-4-producing) fail to stimulate an increase in Fc gamma RII levels. Anti-IL-4 mAb significantly enhanced Fc gamma RII expression by Th2-stimulated B cells indicating that IL-4 was the active, inhibitory, substance produced by the Th2 cells. Supernatants from stimulated Th2 clones inhibited the enhanced expression of Fc gamma RII by LPS-stimulated B cells and this activity was completely reversed by anti-IL-4 mAb. By contrast, supernatants from stimulated Th1 clones further enhanced Fc gamma RII expression by LPS-stimulated B cells. The differential regulation of B cell Fc gamma RII expression by Th subsets may play an important role in the regulation of humoral immunity by altering the sensitivity of B cells to IgG immune complex-mediated inhibition of B cell activation and differentiation in vivo.
Snapper
C M
CM
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Hooley
J J
JJ
Atasoy
U
U
Finkelman
F D
FD
Paul
W E
WE
D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte; D001402:B-Lymphocytes / Q000378:metabolism*; D001667:Binding, Competitive; D002460:Cell Line; D005260:Female; D005803:Genes, Immunoglobulin; D007074:Immunoglobulin G / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000096:biosynthesis / Q000502:physiology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology*
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D007074:Immunoglobulin G; D007378:Interleukins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D012333:RNA, Messenger; D011961:Receptors, Fc; D017452:Receptors, IgG; D015847:Interleukin-4; D007371:Interferon-gamma