Background: Since the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) remains unclear, the rationale for current IgAN therapies is still obscure. Recent studies have shown that galactose-deficient IgA1 (GdIgA1) plays a critical role in the pathogenesis of IgAN and can be a non-invasive IgAN biomarker, although the origin of the pathogenic cells producing GdIgA1 is unknown. We examined the cell types and localization of pathogenic cells in IgAN-prone mice.
Methods: We transplanted bone marrow (BM) or spleen cells with or without specific cell types from IgAN-prone mice, which have many features similar to human IgAN, to identify cell types responsible for the IgAN phenotype and to determine their localization.
Results: BM transplantation and whole spleen cell transfer from IgAN-prone mice reconstituted IgAN in normal and severe combined immunodeficiency mice. Depletion of CD90(+) spleen cells had no affect on reconstitution, whereas CD19(+) B cells from the spleen were sufficient to reconstitute IgAN in both recipients.
Conclusions: These results indicate that CD19(+) B cells, which can regulate nephritogenic IgA production in a T-cell-independent manner, are responsible for the disease and are disseminated in peripheral lymphoid organs.