Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions

K P Knobeloch; M D Wright; A F Ochsenbein; O Liesenfeld; J Löhler; R M Zinkernagel; I Horak; Z Orinska

doi:10.1128/MCB.20.15.5363-5369.2000

Targeted inactivation of the tetraspanin CD37 impairs T-cell-dependent B-cell response under suboptimal costimulatory conditions

Mol Cell Biol. 2000 Aug;20(15):5363-9. doi: 10.1128/MCB.20.15.5363-5369.2000.

Authors

K P Knobeloch¹, M D Wright, A F Ochsenbein, O Liesenfeld, J Löhler, R M Zinkernagel, I Horak, Z Orinska

Affiliation

¹ Department of Molecular Genetics, Institute of Molecular Pharmacology, Free University of Berlin, Berlin, Hamburg, Germany.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antigens, CD / genetics*
Antigens, CD / immunology*
Antigens, Neoplasm*
B-Lymphocytes / immunology*
B-Lymphocytes / physiology
Bone Marrow / immunology
Ficoll / analogs & derivatives
Ficoll / immunology
Gene Silencing
Glycoproteins / genetics*
Glycoproteins / immunology*
Haptens
Hemocyanins / immunology
Histocompatibility Antigens Class II / immunology
Histocompatibility Antigens Class II / metabolism
Immunization
Immunoglobulin G / immunology
Mice
Mice, Mutant Strains
Recombination, Genetic
Rhabdoviridae Infections / immunology
Strongylida Infections / immunology
T-Lymphocytes / immunology*
T-Lymphocytes / physiology
Tetraspanins
Th1 Cells / immunology
Th1 Cells / parasitology
Th2 Cells / immunology
Th2 Cells / parasitology
Trinitrobenzenes / immunology

Substances

Antigens, CD
Antigens, Neoplasm
CD37 protein, human
Cd37 protein, mouse
Glycoproteins
Haptens
Histocompatibility Antigens Class II
Immunoglobulin G
TNP-ficoll
Tetraspanins
Trinitrobenzenes
trinitrophenyl keyhole limpet hemocyanin
Ficoll
Hemocyanins