IL-4 induces Fas resistance in B cells.
Activated B cells express Fas (CD95) and are targets for apoptosis induced by CD4+ Th1 effector cells that kill in a Fas-dependent fashion. We report here that IL-4 reverses the susceptibility to Fas-mediated apoptosis that characterizes CD40-stimulated primary B cells. IL-4-induced Fas resistance is not associated with an alteration in the elevated level of Fas expression produced by CD40 ligand and does not depend on additional receptor-mediated signals. However, IL-4-induced resistance to Th1 cell-mediated cytotoxicity (Th1-CMC) develops more slowly than resistance mediated by surface Ig and is not affected by protein kinase C depletion, unlike anti-Ig-induced Fas resistance. By these two criteria, IL-4-and anti-Ig-induced resistance to Th1-CMC appear to be driven through distinct mechanisms; in keeping with this, suboptimal doses of IL-4 and anti-Ig act in synergy to induce marked protection against Th1-CMC. An important role for IL-4-induced Fas resistance is suggested by the observation that sera from IL-4-overexpressing transgenic mice contain autoreactive Abs.
Foote
L C
LC
Department of Microbiology, Boston University Medical Center, MA 02118, USA.
Howard
R G
RG
Marshak-Rothstein
A
A
Rothstein
T L
TL
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D023201:CD40 Ligand; D003602:Cytotoxicity, Immunologic; D015847:Interleukin-4 / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011493:Protein Kinase C / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000502:physiology*
D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D023201:CD40 Ligand; D015847:Interleukin-4; D011493:Protein Kinase C