Constitutive expression of the B7h ligand for inducible costimulator on naive B cells is extinguished after activation by distinct B cell receptor and interleukin 4 receptor-mediated pathways and can be rescued by CD40 signaling.
The recently described ligand-receptor pair, B7h-inducible costimulator (ICOS), is critical for germinal center formation and antibody responses. In contrast to the induced expression of the related costimulatory ligands B7.1 and B7.2, B7h is constitutively expressed on naive B cells and is surprisingly extinguished after antigen engagement and interleukin (IL)-4 cytokine signaling. Although signaling through both B cell receptor (BCR) and IL-4 receptor (R) converge on the extinction of B7h mRNA levels, BCR down-regulation occurs through Ca2+ mobilization, whereas IL-4R down-regulation occurs through a distinct Stat6-dependent pathway. During antigen-specific B cell activation, costimulation through CD40 signaling can reverse both BCR- and IL-4R-mediated B7h down-regulation. These data suggest that the CD40-CD40 ligand signaling pathway regulates B7h expression on activated B cells and may control whether antigen-activated B cells can express B7h and costimulate cognate antigen-activated T cells through ICOS.
Liang
Linda
L
Division of Immunology, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Porter
Evelyn M
EM
Sha
William C
WC
D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018858:Germinal Center / Q000166:cytology / Q000378:metabolism; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D019948:Receptors, Interleukin-4 / Q000378:metabolism*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D019013:CD40 Antigens; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008024:Ligands; D011506:Proteins; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D023201:CD40 Ligand; D015847:Interleukin-4; D002118:Calcium