Differences between human and mouse igm fc receptor (Fcμr)

Abstract

Both non‐immune “natural” and antigen‐induced “immune” IgM are important for protection against pathogens and for regulation of immune responses to self‐antigens. Since the bona fide IgM Fc receptor (FcμR) was identified in humans by a functional cloning strategy in 2009, the roles of FcμR in these IgM effector functions have begun to be explored. In this short essay, we describe the differences between human and mouse FcμRs in terms of their identification processes, cellular distributions and ligand binding activities with emphasis on our recent findings from the mutational analysis of human FcμR. We have identified at least three sites of human FcμR, i.e., Asn66 in the CDR2, Lys79 to Arg83 in the DE loop and Asn109 in the CDR3, responsible for its constitutive IgM‐ligand binding. Results of computational structural modeling analysis are consistent with these mutational data and a model of the ligand binding, Ig‐like domain of human FcμR is proposed. Serendipitously, substitution of Glu41 and Met42 in the CDR1 of human FcμR with mouse equivalents Gln and Leu, either single or more prominently in combination, enhances both the receptor expression and IgM binding. These findings would help in the future development of preventive and therapeutic interventions targeting FcμR.