In IgA nephropathy (IgAN), elevated levels of the circulating autoantigen, galactose-deficient IgA1, are critical to disease pathogenesis. Abnormal B-cell glycosylation pathways produce the autoantigen that, upon recognition by autoantibodies, forms immune complexes. Genetic as well as in vitro, in vivo, and human immunologic studies identified APRIL (a proliferation-inducing ligand) and BAFF (B-cell activating factor) as key cytokines controlling B-cell development and differentiation of antibody-secreting cells.