Targeted gene disruption reveals a role for natural secretory IgM in the maturation of the primary immune response

Abstract

Accelerated development of the secondary immune response may be attributable in part to the rapid delivery of antigen to lymphoid follicles by circulating antibody elicited on primary immunization. Here we provide evidence indicating that the nonspecific IgM present in naive mice (natural antibody) plays a role in the acceleration of the primary response. Targeted deletion of the Ig s polyadenylation site by use of Cre recombinase allowed the creation of mice that, although harboring a normal number of B cells expressing surface IgM, completely lacked serum IgM while retaining the other Ig isotypes. These mice retained a broadly normal B lymphocyte distribution (although containing a somewhat expanded peritoneal B1a subset) but exhibited substantial delays in mounting affinity-matured IgG responses to T cell-dependent antigens. The T cell-independent response, however, was augmented. The data indicate that the IgM present before antigen challenge (as well, possibly, as that elicited immediately after immunization) accelerates maturation of the primary response, presumably by complexing with the antigen and facilitating lymphocyte activation and͞or antigen trapping.

Non-HLA-Type Endothelial Cell Reactive Alloantibodies in Pre-Transplant Sera of Kidney Recipients Trigger Apoptosis

“…These Abs specifically bind apoptotic EC (28). On the other hand, the development of specific IgG is also accelerated by the natural IgM Abs present in serum before antigen encounter (29). Therefore, it can be also hypothesized that the presence of AECA reflects the overall humoral alloreactivity of patients.…”

Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse

“…IgM antibodies are involved in numerous immunological functions including protection against infection, 1-3 prevention of autoimmunity, 4,5 B-cell homeostasis [6][7][8] and immunosurveillance against tumors. 9,10 IgM biological roles also include opsonization of apoptotic cells, resulting in accelerated clearance by phagocytic cells.…”

Cutting Edge: Selection of B Lymphocyte Subsets Is Regulated by Natural IgM

“…The generation of S Ϫ mice has been described previously (2). Mice were backcrossed onto C57BL/6 mice for six generations and kept under specific pathogen-free conditions.…”

“…N atural serum IgM provides a first defense against infection and accelerates the development of the primary immune response (1,2). Mice deficient in serum IgM (S Ϫ ) 3 also have an elevated response to T-independent Ags, an expanded B1a cell subset, and an increased propensity to develop IgG autoantibodies (3,4).…”