Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions.
CD37 is a membrane protein of the tetraspanin superfamily, which includes CD9, CD53, CD63, CD81, and CD82. Many of these molecules are expressed on leukocytes and have been implicated in signal transduction, cell-cell interactions, and cellular activation and development. We generated and analyzed mice deficient for CD37. Despite the high expression of CD37 on cells of the immune system, no changes in development and cellular composition of lymphoid organs were observed in mice lacking CD37. Analyses of humoral immune responses revealed a reduced level of immunoglobulin G1 (IgG1) in the sera of nonimmunized mice and an alteration of responses to T-cell-dependent antigens. Antibody responses to model antigen administered in the absence of adjuvant and to viral infections were generally poor in CD37-deficient mice. These poor antibody responses could be overcome by the immunization of antigen together with adjuvant. These results suggest a role for CD37 in T-cell-B-cell interactions which manifests itself under suboptimal costimulatory conditions.
Knobeloch
K P
KP
Department of Molecular Genetics, Institute of Molecular Pharmacology, Free University of Berlin, Berlin, Hamburg, Germany.
Wright
M D
MD
Ochsenbein
A F
AF
Liesenfeld
O
O
Löhler
J
J
Zinkernagel
R M
RM
Horak
I
I
Orinska
Z
Z
D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology*; D000951:Antigens, Neoplasm; D001402:B-Lymphocytes / Q000276:immunology* / Q000502:physiology; D001853:Bone Marrow / Q000276:immunology; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D020868:Gene Silencing; D006023:Glycoproteins / Q000235:genetics* / Q000276:immunology*; D006241:Haptens; D006433:Hemocyanins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D011995:Recombination, Genetic; D018353:Rhabdoviridae Infections / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D059470:Tetraspanins; D018417:Th1 Cells / Q000276:immunology / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology / Q000469:parasitology; D014301:Trinitrobenzenes / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; C059071:CD37 protein, human; C504565:Cd37 protein, mouse; D006023:Glycoproteins; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; C020529:TNP-ficoll; D059470:Tetraspanins; D014301:Trinitrobenzenes; C054401:trinitrophenyl keyhole limpet hemocyanin; D005362:Ficoll; D006433:Hemocyanins