The Old but New IgM Fc Receptor (FcμR)

Abstract

IgM is the first Ig isotype to appear during phylogeny, ontogeny and the immune response. The importance of both pre-immune "natural" and antigen-induced "immune" IgM antibodies in immune responses to pathogens and self-antigens has been established by studies of mutant mice deficient in IgM secretion. Effector proteins interacting with the Fc portion of IgM, such as complement and complement receptors, have thus far been proposed, but fail to fully account for the IgM-mediated immune protection and regulation of immune responses. Particularly, the role of the Fc receptor for IgM (FcμR) in such effector functions has not been explored until recently. We have identified an authentic FcμR in humans using a functional cloning strategy and subsequently in mice by RT-PCR and describe here its salient features and the immunological consequences of FcμR deficiency in mice. Since the FcμR we cloned was identical to Toso or Fas inhibitory molecule 3 (FAIM3), there have been spirited debates regarding the real function of FcμR/Toso/FAIM3 and we will also comment on this topic.

Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM

“…Deposited IgM may also have pathologic effects that are not mediated through the complement system. There is a receptor for IgM, for example, and this receptor may mediate a mild pathologic effect, although the expression and function of this receptor is incompletely understood . Nevertheless, the overall effect of IgM in this model seems to be modest.…”

Secreted IgM: New tricks for an old molecule

“…A splice variant of the FcµR lacking the transmembrane exon seems to encode a soluble form of the receptor. It has been proposed that the soluble receptor serves as a “decoy” for sIgM‐interaction with cell; however, more follow‐up studies are required to confirm these findings and their biological significance.…”

“…It has been proposed that the soluble receptor serves as a "decoy" for sIgM-interaction with cell 113,136 ; however, more follow-up studies are required to confirm these findings and their biological significance.…”

Rational Design and In Vivo Characterization of Vaccine Adjuvants

“…Both mice and humans express the FcR for IgM (FcμR or TOSO). 120 However, in contrast to humans, mice lack FcαRI. Humans express the Fc receptors for IgG, FcγRI, FcγRIIA, FcγRIIC, and hFcγRIIIA, which are activating, and FcγRIIB, which is inhibitory.…”