The Long Elusive IgM Fc Receptor, FcμR

Abstract

IgM exists as both a monomer on the surface of B cells and a pentamer secreted by plasma cells. Both preimmune “natural” and antigen-induced “immune” IgM antibodies are important for protective immunity and for immune regulation of autoimmune processes by recognizing pathogens and self-antigens. 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 protection and regulation. A major reason for this deficit in our understanding of IgM function seems to be lack of data on a long elusive Fc receptor for IgM (FcμR). We have recently identified a bona fide FcμR in both humans and mice. In this article we briefly review what we have learned so far about FcμR.

Sialylation of N-Linked Glycans Influences the Immunomodulatory Effects of IgM on T Cells

“…Fca/mR and pIgR bind both IgM and IgA (pIgR requires J chain for binding Abs) and are expressed in nonhematopoietic tissues and on B cells and macrophages (Fca/mR) or on the basolateral surface of mucous epithelium and duct of excretory glands (pIgR). The FcmR is the only FcR constitutively expressed on both CD4-positive and CD8-positive T cells that selectively binds IgM with very high affinity, and is also expressed on B lymphocytes (33)(34)(35)(36). It binds pentameric IgM 100 times more strongly than monomeric IgM (34) and is rapidly internalized upon IgM binding (35).…”

Secreted IgM: New tricks for an old molecule

“…Interestingly, binding of sIgM to the Fcα/µR was greatly reduced when pentameric sIgM was complexed with AIM . The Fcα/µR appears to be expressed predominantly on antigen‐presenting cells, including macrophages, and to be particularly abundant on FDC, while it is not expressed on granulocytes, T cells or NK cells …”

“…In humans, the receptor was shown to be expressed on T and NK cells, but not on myeloid cells . Expression on human T cells was higher on α/β T cells than γ/δ T cells, and higher on CD4+ than on CD8+ T cells . It will be important to understand the functional significance of these expression differences between mice and humans.…”

Antibody Isotypes for Tumor Immunotherapy

“…The Fc receptor for IgM is called FcµR and is found exclusively on lymphocytes (B, T and NK cells) in men and only on B cells in mice. FcµR shows a unique immunoreceptor tyrosine-based inhibition motif (ITIM) and immunoreceptor tyrosine-based activation motif (ITAM) pattern suggesting that the receptor may have the ability to act as a dual signal transmitter [7]. However, rather little is known about the IgM FcR and its role in immunity.…”

“…C1q of the complement cascade) or with specialized receptors on immune effector cells. In addition to classical Fc receptors for IgA, IgE and IgG [4,5,6], a receptor for IgM [7], a common receptor for IgA and IgM (Fcα/µR) [8], and a family of Fc receptor-like molecules (FcRL) have been distinguished [9]. …”