Mice lacking IgA exhibit defective IgG antibody responses to polysaccharide conjugate vaccine (84.14)

Abstract

Abstract Streptococcus pneumoniae is a leading cause of global disease. While capsular polysaccharide conjugate vaccines have decreased disease burden; a portion of the population remains unresponsive to vaccination. In order to understand the mechanisms responsible vaccine non-responsiveness, studies have been performed using mice with a targeted gene deletion that causes lack of IgA but few alterations in expression of other Ig isotypes. Surprisingly, IgA-/- mice were found nonetheless to exhibit specific defects in both IgA and IgG antibody responses to the polysaccharide (PS) component of pneumococcal conjugate vaccine. Neither IgM anti-PS responses nor IgG antibody responses to the protein component of the conjugate vaccine were affected. Furthermore, IgA-/- mice expressed fewer peritoneal B1a cells. As B1a and marginal zone B cells are considered to be the primary cell types that respond to polysaccharide antigens, this might to some extent explain the decreased anti-PS serum antibody titers seen in IgA-/- mice. Studies using bone marrow chimeras showed that reconstitution of IgA-/- mice with IgA+/+ B cells failed to restore antibody responsiveness to the PS component of the conjugate vaccine. Taken together, these results indicate that a defect in IgA expression affects B cell homeostasis, which is partially influenced by the environment that is present during B cell activation. (Supported by NIH grants RO1 41715 and R21 83878).