Impaired germinal center formation and recall T-cell-dependent immune responses in mice lacking the costimulatory ligand B7-H2.
B7-H2, which is expressed constitutively on B cells and binds the inducible costimulator (ICOS) on antigen-activated T cells, is a member of the B7 family of costimulatory ligands. We have inactivated B7-H2 in the mouse. B7-H2-/- mice generate normal populations of B and T cells in their various lymphoid organs but have lower basal levels of heavy chain class-switched antibodies in their sera. These mice are able to mount normal immune responses to both type I and type II T-cell-independent antigens. However, their pattern of responses to a T-cell-dependent antigen is altered, with greatly reduced production of antigen-specific heavy chain class-switched antibodies, the levels of which could not be elevated even with repeated immunizations. This suggests a critical role for B7-H2 in the recall phases of the immune response. Germinal center formation is also impaired in the mutant mice. While B cells from the mutant mice could response normally to anti-IgM, anti-CD40, and lipopolysaccharide stimulation, the production of T-helper-type II cytokines such as interleukin-4 (IL-4) and IL-10 by primed CD4+ T cells from mutant mice were reduced. This indicated that the defects in humoral responses and germinal center formation in B7-H2-deficient mice are due to the lack of T-cell-mediated help to the B cells. Hence, B7-H2 on B cells is important for recruiting T-cell help via its interaction with ICOS and plays a critical role in costimulating humoral immune responses.
Wong
Siew-Cheng
SC
Institute of Molecular and Cell Biology, Singapore, Republic of Singapore.
Oh
Edwin
E
Ng
Chee-Hoe
CH
Lam
Kong-Peng
KP
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007156:Immunologic Memory / Q000276:immunology; D060945:Inducible T-Cell Co-Stimulator Ligand; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008024:Ligands; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D019013:CD40 Antigens; D002352:Carrier Proteins; C400230:Icosl protein, mouse; D007136:Immunoglobulins; D060945:Inducible T-Cell Co-Stimulator Ligand; D008024:Ligands; D008070:Lipopolysaccharides; D011506:Proteins; D016753:Interleukin-10; D015847:Interleukin-4