Abstract
Circulating immunoglobulin M (IgM) exists in a pentameric form, possessing a polyreactive nature that responds not only to foreign antigens but also to autoantigens; thus, it is involved in both beneficial and detrimental immune responses, including protection from infection and the progression of autoimmunity. On the other hand, IgM also behaves as a carrier of the apoptosis inhibitor of macrophage (AIM) protein, storing a large amount of the inactivated form of AIM in the blood through this association. Under different disease conditions, AIM can dissociate from IgM locally or systemically to exert its function, inducing the removal of various biological debris such as excess fat, bacteria, cancer cells or dead cell debris. Most typically, upon induction of acute kidney injury (AKI), IgM-free AIM is filtered by the glomerulus in the kidney, which stimulates the clearance of intraluminal dead cells debris at the obstructed proximal tubules, thereby facilitating the repair of kidney injury. Interestingly, cats exhibit a deficiency in AIM release from IgM, which may increase their susceptibility to renal failure. Conversely, association with AIM inhibits IgM binding to the Fcα/μ receptor on follicular dendritic cells at the splenic germinal center, thereby protecting the IgM immune complex from Fcα/μ receptor-mediated internalization, which supports IgM-dependent antigen presentation to B cells and stimulates high-affinity IgG antibody production. The regulation of AIM-IgM binding, resulting from the discovery of reciprocal actions between AIM and IgM, could lead to the development of novel therapies against different diseases.