Mice deficient for the CD40 ligand.
To study the potential roles of CD40L in immune responses, we generated CD40L-deficient mice by gene targeting. Similar to the effects of CD40L mutations in humans (hyper-IgM syndrome), CD40L-deficient mice have a decreased IgM response to thymus-dependent antigens, fail altogether to produce an antigen-specific IgG1 response following immunization, yet respond normally to a T-independent antigen, TNP-Ficoll. Moreover, these mice do not develop germinal centers in response to thymus-dependent antigens, suggesting an inability to develop memory B cell responses. Although CD40L-deficient mice have low levels of most circulating immunoglobulin isotypes, they do not exhibit the spontaneous hyper-IgM syndrome seen in humans, at least up to 12 weeks of age. In summary, our study confirms the important role of CD40-CD40L interactions in thymus-dependent humoral immune responses and germinal center formation.
Xu
J
J
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510.
Foy
T M
TM
Laman
J D
JD
Elliott
E A
EA
Dunn
J J
JJ
Waldschmidt
T J
TJ
Elsemore
J
J
Noelle
R J
RJ
Flavell
R A
RA
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D006942:Hypergammaglobulinemia / Q000276:immunology; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000235:genetics; D007074:Immunoglobulin G / Q000097:blood / Q000235:genetics; D007075:Immunoglobulin M / Q000097:blood / Q000235:genetics; D007156:Immunologic Memory; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D013950:Thymus Gland / Q000276:immunology
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D023201:CD40 Ligand