Circulating galactose-deficient IgA1+ lambda+ B cells that preferentially express mucosal homing receptors are associated with the progression of IgA nephropathy

Abstract B cells play a central role in the pathogenesis of immunoglobulin A nephropathy (IgAN) through the production of galactose-deficient IgA1 (Gd-IgA1). Accumulating evidence suggests that multiple circulating B-cell subsets abnormally distributed in IgAN and are involved in abnormal humoral immune responses. It has been observed that Gd-IgA1 + cells in the peripheral blood of IgAN patients predominantly express lambda (λ) light chains, which is consistent with reports that λ chain deposition predominates in the mesangia of glomeruli in IgAN patients. Gd-IgA + λ + cells preferentially express CCR9 and CCR10 and tend to home to mucosa-associated lymphoid tissue, which may promote Gd-IgA1-λ production and the progression of IgAN during mucosal infections. In humans, plasma cells within the intestinal mucosa naturally exhibit a predominance of λ light chain expression. Given that the pathogenesis of IgAN is closely linked to the dysregulation of the intestinal mucosal immune system, it is hypothesized that this immune disturbance may further amplify the local preference for λ in the intestine. This mini-review summarizes changes in the circulating B-cell profile and recent research progress on λ in IgAN, and explores the potential mechanisms underlying λ predominance in IgAN. These findings may contribute to a deeper understanding of the pathogenesis of IgAN and provide new insights for future research directions.