Differences between human and mouse igm fc receptor (Fcμr)

Hiromi Kubagawa; Christopher M. Skopnik; Khlowd Al‐qaisi; Rosaleen A. Calvert; Kazuhito Honjo; Yoshiki Kubagawa; Ruth Teuber; Pedram Mahmoudi Aliabadi; Philipp Enghard; Andreas Radbruch; Brian J. Sutton

doi:10.3390/ijms22137024

Differences between human and mouse igm fc receptor (Fcμr)

Hiromi Kubagawa^*, Christopher M. Skopnik, Khlowd Al‐qaisi, Rosaleen A. Calvert, Kazuhito Honjo, Yoshiki Kubagawa, Ruth Teuber, Pedram Mahmoudi Aliabadi, Philipp Enghard, Andreas Radbruch, Brian J. Sutton

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Article number	7024
Journal	International Journal of Molecular Sciences
Volume	22
Issue number	13
DOIs	https://doi.org/10.3390/ijms22137024
Publication status	Published - 1 Jul 2021

Keywords

3D structure
Computational structural model
FcR
Fcα/μR
FcμR
IgM binding
PIgR
Species difference

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10.3390/ijms22137024

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@article{609fb92b056d45fead06041dd2e16dad,

title = "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.",

keywords = "3D structure, Computational structural model, FcR, Fcα/μR, FcμR, IgM binding, PIgR, Species difference",

author = "Hiromi Kubagawa and Skopnik, {Christopher M.} and Khlowd Al‐qaisi and Calvert, {Rosaleen A.} and Kazuhito Honjo and Yoshiki Kubagawa and Ruth Teuber and Aliabadi, {Pedram Mahmoudi} and Philipp Enghard and Andreas Radbruch and Sutton, {Brian J.}",

note = "Funding Information: Funding: Funded by the Deutsches Rheuma‐Forschungszentrum Institutional funds (to H.K.) and BBSRC Project Grant (BB/K006142/1) (to B.J.S.) Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

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doi = "10.3390/ijms22137024",

language = "English",

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T1 - Differences between human and mouse igm fc receptor (Fcμr)

AU - Kubagawa, Hiromi

AU - Skopnik, Christopher M.

AU - Al‐qaisi, Khlowd

AU - Calvert, Rosaleen A.

AU - Honjo, Kazuhito

AU - Kubagawa, Yoshiki

AU - Teuber, Ruth

AU - Aliabadi, Pedram Mahmoudi

AU - Enghard, Philipp

AU - Radbruch, Andreas

AU - Sutton, Brian J.

N1 - Funding Information: Funding: Funded by the Deutsches Rheuma‐Forschungszentrum Institutional funds (to H.K.) and BBSRC Project Grant (BB/K006142/1) (to B.J.S.) Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7/1

Y1 - 2021/7/1

N2 - 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.

AB - 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.

KW - 3D structure

KW - Computational structural model

KW - FcR

KW - Fcα/μR

KW - FcμR

KW - IgM binding

KW - PIgR

KW - Species difference

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U2 - 10.3390/ijms22137024

DO - 10.3390/ijms22137024

M3 - Article

AN - SCOPUS:85108789600

SN - 1661-6596

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 13

M1 - 7024

ER -

Differences between human and mouse igm fc receptor (Fcμr)

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Keywords

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