TARGETED GENE DISRUPTION REVEALS A ROLE FOR NATURAL SECRETORY IGM IN THE MATURATION OF THE PRIMARY IMMUNE-RESPONSE

Accelerated development of the secondary immune response may be attrib utable in part to the rapid delivery of antigen to lymphoid follicles by circulating antibody elicited on primary immunization. Here we prov ide evidence indicating that the nonspecific IgM present in naive mice (natural antibody) plays a role in the acceleration of the primary re sponse. Targeted deletion of the Ig mu(s) polyadenylation site by use of Cre recombinase allowed the creation of mice that, although harbori ng a normal number of B cells expressing surface IgM, completely lacke d serum IgM while retaining the other Ig isotypes. These mice retained a broadly normal B lymphocyte distribution (although containing a som ewhat expanded peritoneal Bla subset) but exhibited substantial delays in mounting affinity-matured IgG responses to T cell-dependent antige ns, The T cell-independent response, however, was augmented. The data indicate that the IgM present before antigen challenge las well, possi bly, as that elicited immediately after immunization) accelerates matu ration of the primary response, presumably by complexing with the anti gen and facilitating lymphocyte activation and/or antigen trapping.