IgA nephropathy (IgAN), the common primary
glomerulonephritis, is a tonsillar
focal infection characterized by the qualitative abnormality of
IgA in circulation and
IgA deposition in the renal mesangium. Mesangial deposition of
IgA, which is composed predominantly of poorly galactosylated polymeric
IgA1 (pIgA1), seems to be the initiating event in the pathogenesis of IgAN. The origin of poorly galactosylated
IgA, however, remains unclear. Recent studies suggest that the mesangial polymeric
IgA1 deposition could be derived from mucosally primed plasma cells. B cells may undergo
IgA class switching to acquire the expression of
IgA via T-cell-dependent or T-cell-independent pathways in mucosa-associated lymphoid tissue and then differentiate to
IgA plasma cells or home in on systemic sites. Dendritic cells, including plasmacytoid dendritic cells and another type of
antigen-retaining cell, follicular dendritic cells, have an irreplaceable role in
IgA class-switch mechanisms by producing
IgA-inducing signals. Furthermore, an increased number of pIgA1-secreting plasma cells in the bone marrow and tonsil, as well as increased
IgA class switching, have been found in IgAN, providing a link between the mucosal immunity and IgAN. The favorable effect of
tonsillectomy on patients with IgAN showed that tonsillar
focal infection may be closely related to pIgA1 deposition in glomerular mesangium of patients with IgAN and at least a part of pIgA1 may originate from affected tonsils. Therefore, the indication for
tonsillectomy should be considered in patients with
IgA nephropathy, especially at a mild or early stage, to prevent future renal deterioration. In this paper, we focus on
IgA class switching and the role of tonsils with
focal infection in IgAN.