Wehbi B, et al. - Given that IgA glomerular mesangial deposition characterizes IgA nephropathy (IgAN), researchers sought for its pathogenesis. They examined if a hypogalactosylated hinge region (found in most mesangial IgA1 in human IgAN) is required for IgA deposition, using humanized transgenic mouse models, demonstrating that hinge hypoglycosylation was not mandatory for deposition. They compared mice able to produce high-affinity mature IgA antibodies with mice lacking affinity maturation in order to examine whether low-affinity IgA produced by innate-like B cells might also yield mesangial deposits. It was noted that in the mesangium, the low-affinity IgA can deposit and activate complement, that it is particularly prone to provoke glomerular cell thickening, and that it can initiate nephrotoxicity. Findings, thereby, propose a new perspective concerning glomerular IgA deposits involving innate-like antibody responses.