Background IgA nephropathy (IgAN) primary glomerulonephritis is characterized by the deposition of circulating immune complexes composed of polymeric IgA1 molecules with altered O-glycans (Gd-IgA1) and anti-glycan antibodies in the kidney mesangium. The mesangial IgA deposits and serum IgA1 contain predominantly l light (L) chains, but the nature and origin of such IgA remains enigmatic. Methods We analyzed l L chain expression in peripheral blood B cells of 30 IgAN patients, 30 healthy controls (HCs), and 18 membranous nephropathy patients selected as disease controls (non-IgAN). Results In comparison to HCs and non-IgAN patients, peripheral blood surface/membrane bound (mb)- Gd-IgA11 cells from IgAN patients express predominantly l L chains. In contrast, total mb-IgA1, mb- IgG1, and mb-IgM1 cells were preferentially positive for kappa (k) L chains, in all analyzed groups. Although minor in comparison to k L chains, l L chain subsets of mb-IgG1, mb-IgM1, and mb-IgA1 cells were significantly enriched in IgAN patients in comparison to non-IgAN patients and/or HCs. In contrast to HCs, the peripheral blood of IgAN patients was enriched with l1 mb-Gd-IgA11, CCR101, and CCR91 cells, which preferentially home to the upper respiratory and digestive tracts. Furthermore, we observed that mb-Gd-IgA11 cell populations comprise more CD1381 cells and plasmablasts (CD381) in comparison to total mb-IgA1 cells. Conclusions Peripheral blood of IgAN patients is enriched with migratory l1 mb-Gd-IgA11 B cells, with the potential to home to mucosal sites where Gd-IgA1 could be produced during local respiratory or digestive tract infections.
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