Cutting edge: critical role of inducible costimulator in germinal center reactions.
Inducible costimulator (ICOS) is a new member of the CD28/CTLA-4 family that is expressed on activated and germinal center (GC) T cells. Recently, we reported that ICOS-deficient mice exhibited profound defects in T cell activation and effector function. Ab responses in a T-dependent primary reaction and in a murine asthma model were also diminished. In the current study, we investigate the mechanism by which ICOS regulates humoral immunity and examine B cell GC reactions in the absence of ICOS. We found that ICOS(-/-) mice, when immunized with SRBC, had smaller GCs. Furthermore, IgG1 class switching in the GCs was impaired. Remarkably, GC formation in response to a secondary recall challenge was completely absent in ICOS knockout mice. These data establish a critical role of ICOS in regulation of humoral immunity.
Section of Immunobiology, Yale University School of Medicine and Howard Hughes Medical Institute, New Haven, CT 06514, USA. chendong@u.washington.edu
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D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D023201:CD40 Ligand / Q000096:biosynthesis; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007117:Immunization, Secondary; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D060889:Inducible T-Cell Co-Stimulator Protein; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D019887:Peanut Agglutinin / Q000096:biosynthesis; D012756:Sheep; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; C556694:Icos protein, mouse; D007074:Immunoglobulin G; D060889:Inducible T-Cell Co-Stimulator Protein; D019887:Peanut Agglutinin; D023201:CD40 Ligand