Bacterial infection and production of immunoglobulin in the tonsil

Immunoglobulin (Ig) isotype switching is the process whereby B cells initially expressing IgM and/or IgD on their surface switch to other Ig heavy-chain loci. We demonstrated that TGF-beta, IL-10 and VIP in the presence of CD40 mAb, can induce isotype switching for IgA in human tonsillar B cells by the generation of switch circular DNA (S alpha/S mu), the induction of alpha germ-line transcripts and a significant amount of IgA production. IgA is the predominant immunoglobulin effector molecule of mucosal immunity that functions as the first line of specific immunologic defense against many microbial pathogens. However, IgA causes IgA nephropathy. We investigated here, whether tonsillar mononuclear cells from patients with IgA nephropathy produce HP-specific IgA and/or IgA-related cytokines by stimulation with components of HP outer membranes (OMHP). HP-specific IgA was predominately induced by tonsillar mononuclear cells of IgA nephropathy, compared to those from chronic tonsillitis. Production of IL-10 and TGF-beta was enhanced by stimulation with OMHP in tonsillar mononuclear cells from IgA nephropathy. These results suggested that local infection of HP and HP-specific IgA induction in the tonsil are associated with pathogens in IgA nephropathy.