Influence of IgA expression on T‐Dependent and T‐Independent antibody responses

Abstract

Individuals with selective IgA deficiency are competent in producing IgG antibodies but often suffer from recurrent respiratory infections with encapsulated bacteria. We examined the immunological basis for this hyper‐susceptibility using an IgA deficient (IgA KO) mouse model. Following i.m. vaccination, WT and IgA KO mice produced similar levels of all antibody isotypes (other than IgA) against T‐dependent antigens, including CRM197 and Influenza HA and NA. However, IgA KO mice were severely defective in producing IgG antibody against T‐independent (TI) antigens such as polysaccharides, polysaccharides conjugated to carrier proteins, although they did produce normal levels of IgM. Inoculation of IL‐12 as an adjuvant during vaccination increased IgG antibody levels in both wild‐type and IgA KO mice to the same relative degree, suggesting a quantitative rather than qualitative defect in TI antigen‐responsive cells in IgA KO mice. Indeed, flow cytometric analyses revealed that IgA KO mice contained significantly fewer peritoneal B‐1a B cells, the cell type thought to be primarily responsible for TI antibody responses. These results could explain the frequent failure of conjugate vaccines to induce protective immunity in IgA‐deficient patients. Further investigations are underway to elucidate the molecular basis for the defective class switching by IgA KO mice in response to TI antigens.RO1 AI41715