MICE DEFICIENT FOR THE CD40 LIGAND

To study the potential roles of CD40L in immune responses, we generate d CD40L-deficient mice by gene targeting. Similar to the effects of CD 40L mutations in humans (hyper-IgM syndrome), CD40L-deficient mice hav e a decreased IgM response to thymus-dependent antigens, fail altogeth er to produce an antigen-specific IgG1 response following immunization , yet respond normally to a T-independent antigen, TNP-Ficoll. Moreove r, these mice do not develop germinal centers in response to thymus-de pendent antigens, suggesting an inability to develop memory B cell res ponses. Although CD40L-deficient mice have low levels of most circulat ing immunoglobulin isotypes, they do not exhibit the spontaneous hyper -IgM syndrome seen in humans, at least up to 12 weeks of age. In summa ry, our study confirms the important role of CD40-CD40L interactions i n thymus-dependent humoral immune responses and germinal center format ion.