The immune responses in CD40-deficient mice: impaired immunoglobulin class switching and germinal center formation.
An engagement of CD40 with CD40 ligand (CD40L) expressed on activated T cells is known to provide an essential costimulatory signal to B cells in vitro. To investigate the role of CD40 in in vivo immune responses, CD40-deficient mice were generated by gene targeting. The significant reduction of CD23 expression on mature B cells and relatively decreased number of IgM bright and IgD dull B cells were observed in the mutant mice. The mutant mice mounted IgM responses but no IgG, IgA, and IgE responses to thymus-dependent (TD) antigens. However, IgG as well as IgM responses to thymus-independent (TI) antigens were normal. Furthermore, the germinal center formation was defective in the mutant mice. These results suggest that CD40 is essential for T cell-dependent immunoglobulin class switching and germinal center formation, but not for in vivo T cell-dependent IgM responses and T cell-independent antibody responses.
Kawabe
T
T
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Naka
T
T
Yoshida
K
K
Tanaka
T
T
Fujiwara
H
H
Suematsu
S
S
Yoshida
N
N
Kishimoto
T
T
Kikutani
H
H
D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D000955:Antigens, T-Independent / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D019013:CD40 Antigens; D017931:DNA Primers / Q000235:genetics; D005260:Female; D018390:Gene Targeting; D006098:Granulocytes; D006801:Humans; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000096:biosynthesis; D007150:Immunohistochemistry; D007589:Job Syndrome / Q000276:immunology; D007958:Leukocyte Count; D008221:Lymphoid Tissue / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000955:Antigens, T-Independent; D019013:CD40 Antigens; D017931:DNA Primers; D007075:Immunoglobulin M