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FCRLA—A Resident Endoplasmic Reticulum Protein that Associates with Multiple Immunoglobulin Isotypes in B Lineage Cells

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IgM and Its Receptors and Binding Proteins

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 408))

Abstract

FCRLA is homologous to receptors for the Fc portion of IgG (FcγR) and is located in the same region of human chromosome one, but has several unusual and unique features. It is a soluble resident ER protein retained in this organelle by unknown mechanisms involving the N-terminal domain, a disordered domain with three Cys residues in close proximity in the human protein. Unlike the FcγRs, FCRLA is not glycosylated and has no transmembrane region. FCRLA is included in this CTMI volume on IgM-binding proteins because it binds IgM in the ER, but quite surprisingly, given the isotype-restricted ligand specificity of the other FcRs, it also binds all other Ig isotypes so far tested, IgG and IgA. In the case of IgM, there is even preferential binding of the secretory and not the transmembrane form. Among B cells, FCRLA is most highly expressed in the germinal center and shows little expression in plasma cells. Based on these observations, we propose that one human FCRLA function is to stop GC B cells from secreting IgM, which would act as a decoy receptor, thus preventing the B cells from capturing antigen, processing it, and presenting the antigen-derived peptides to T follicular helper cells. Without help from these T cells, there would be limited B cell isotype switching, proliferation, and differentiation. On the other hand, FCRLA is downregulated in plasma cells, where IgM secretion is an essential function. FCRLA may also act as a chaperone involved by unknown mechanisms in the proper assembly of Ig molecules of all isotypes.

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Acknowledgements

We thank our many colleagues for insightful discussions, including Tim Wilson, Linda Hendershot, Alexander Taranin, Randall Davis, Hiromi Kubagawa, Ludmilla Mechetina, John Kearney, and Max Cooper. We thank NIH for funding.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    Tessa E. Blackburn

  2. Department of Pathology, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Teresa Santiago

  3. Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA

    Peter D. Burrows

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  1. Tessa E. Blackburn
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  2. Teresa Santiago
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  3. Peter D. Burrows
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Correspondence to Peter D. Burrows .

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Editors and Affiliations

  1. Deutsches Rheumaforschungszentrum, Berlin, Germany

    Hiromi Kubagawa

  2. Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Peter D. Burrows

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Blackburn, T.E., Santiago, T., Burrows, P.D. (2017). FCRLA—A Resident Endoplasmic Reticulum Protein that Associates with Multiple Immunoglobulin Isotypes in B Lineage Cells. In: Kubagawa, H., Burrows, P. (eds) IgM and Its Receptors and Binding Proteins. Current Topics in Microbiology and Immunology, vol 408. Springer, Cham. https://doi.org/10.1007/82_2017_40

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