Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor.
Signals from CD4+ T cells induce two opposite fates in B cells: clonal proliferation of B cells that bind specifically to foreign antigens and clonal deletion of equivalent B cells that bind self-antigens. This B cell fate decision is determined by the concerted action of two surface proteins on activated T cells, CD40-and Fas-ligands (CD40L and FasL), whose effects are switched by signals from the B cell antigen receptor (BCR). Foreign antigens that stimulate the BCR acutely cause CD40L and FasL to promote clonal proliferation. CD40L and FasL trigger deletion, however, when the BCRs become desensitized by chronic stimulation with self-antigens or when BCRs have not bound an antigen. The need for both Fas and CD40L to correctly regulate self-reactive B cell fate may explain the severe autoantibody disorders in Fas- or CD40L-deficient children.
Rathmell
J C
JC
Howard Hughes Medical Institute, Department of Microbiology and Immunology, Stanford University, California 94305, USA.
Townsend
S E
SE
Xu
J C
JC
Flavell
R A
RA
Goodnow
C C
CC
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D001327:Autoimmune Diseases / Q000503:physiopathology; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D053222:Fas Ligand Protein; D007108:Immune Tolerance; D008024:Ligands; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D019013:CD40 Antigens; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D019014:fas Receptor; D023201:CD40 Ligand