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The Appearance and Diversification of Receptors for IgM During Vertebrate Evolution

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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

Three different receptors that interact with the constant domains of IgM have been identified: the polymeric immunoglobulin (Ig) receptor (PIGR), the dual receptor for IgA/IgM (FcαµR) and the IgM receptor (FcµR). All of them are related in structure and located in the same chromosomal region in mammals. The functions of the PIGRs are to transport IgM and IgA into the intestinal lumen and to saliva and tears, whereas the FcαµRs enhance uptake of immune complexes and antibody coated bacteria and viruses by B220+ B cells and phagocytes, as well as dampening the Ig response to thymus-independent antigens. The FcµRs have broad-spectrum effects on B-cell development including effects on IgM homeostasis, B-cell survival, humoral immune responses and also in autoantibody formation. The PIGR is the first of these receptors to appear during vertebrate evolution and is found in bony fish and all tetrapods but not in cartilaginous fish. The FcµR is present in all extant mammalian lineages and also in the Chinese and American alligators, suggesting its appearance with early reptiles. Currently the FcαµR has only been found in mammals and is most likely the evolutionary youngest of the three receptors. In bony fish, the PIGR has either 2, 3, 4, 5 or 6 extracellular Ig-like domains, whereas in amphibians, reptiles and birds it has 4 domains, and 5 in all mammals. The increase in domain number from 4 to 5 in mammals has been proposed to enhance the interaction with IgA. Both the FcαµRs and the FcµRs contain only one Ig domain; the domain that confers Ig binding. In both of these receptors this domain shows the highest degree of sequence similarity to domain 1 of the PIGR. All Ig domains of these three receptors are V type domains, indicating they all have the same origin although they have diversified extensively in function during vertebrate evolution by changing expression patterns and cytoplasmic signaling motifs.

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References

  • Akula S, Mohammadamin S, Hellman L (2014) Fc receptors for immunoglobulins and their appearance during vertebrate evolution. PLoS ONE 9:e96903

    Article  PubMed  PubMed Central  Google Scholar 

  • Altman MO, Bennink JR, Yewdell JW, Herrin BR (2015) Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity. Elife 4

    Google Scholar 

  • Amemiya CT, Alfoldi J, Lee AP, Fan S, Philippe H, Maccallum I, Braasch I, Manousaki T, Schneider I, Rohner N, Organ C, Chalopin D, Smith JJ, Robinson M, Dorrington RA, Gerdol M, Aken B, Biscotti MA, Barucca M, Baurain D, Berlin AM, Blatch GL, Buonocore F, Burmester T, Campbell MS, Canapa A, Cannon JP, Christoffels A, de Moro G, Edkins AL, Fan L, Fausto AM, Feiner N, Forconi M, Gamieldien J, Gnerre S, Gnirke A, Goldstone JV, Haerty W, Hahn ME, Hesse U, Hoffmann S, Johnson J, Karchner SI, Kuraku S, Lara M, Levin JZ, Litman GW, Mauceli E, Miyake T, Mueller MG, Nelson DR, Nitsche A, Olmo E, Ota T, Pallavicini A, Panji S, Picone B, Ponting CP, Prohaska SJ, Przybylski D, Saha NR, Ravi V, Ribeiro FJ, Sauka-Spengler T, Scapigliati G, Searle SM, Sharpe T, Simakov O, Stadler PF, Stegeman JJ, Sumiyama K, Tabbaa D, Tafer H, Turner-Maier J, van Heusden P, White S, Williams L, Yandell M, Brinkmann H, Volff JN, Tabin CJ, Shubin N, Schartl M, Jaffe DB, Postlethwait JH, Venkatesh B, di Palma F, Lander ES, Meyer A, Lindblad-Toh K (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature 496:311–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bakema JE, van Egmond M (2011) The human immunoglobulin A Fc receptor FcαRI: a multifaceted regulator of mucosal immunity. Mucosal Immunol 4:612–624

    Article  CAS  PubMed  Google Scholar 

  • Bakos MA, Kurosky A, Goldblum RM (1991) Characterization of a critical binding site for human polymeric Ig on secretory component. J Immunol 147:3419–3426

    CAS  PubMed  Google Scholar 

  • Blank U, Ra C, Miller L, White K, Metzger H, Kinet JP (1989) Complete structure and expression in transfected cells of high affinity IgE receptor. Nature 337:187–189

    Article  CAS  PubMed  Google Scholar 

  • Boudinot P, Zou J, Ota T, Buonocore F, Scapigliati G, Canapa A, Cannon J, Litman G, Hansen JD (2014) A tetrapod-like repertoire of innate immune receptors and effectors for coelacanths. J Exp Zool B Mol Dev Evol 322:415–437

    Article  CAS  PubMed  Google Scholar 

  • Brandtzaeg P, Johansen FE (2001) Confusion about the polymeric Ig receptor. Trends Immunol 22:545–546

    Article  CAS  PubMed  Google Scholar 

  • Casanova JE, Breitfeld PP, Ross SA, Mostov KE (1990) Phosphorylation of the polymeric immunoglobulin receptor required for its efficient transcytosis. Science 248:742–745

    Article  CAS  PubMed  Google Scholar 

  • Choi SC, Wang H., Tian L, Murakami Y, Shin DM, Borrego F, Morse HC, III, Coligan JE (2013) Mouse IgM Fc receptor, FCMR, promotes B cell development and modulates antigen-driven immune responses. J Immunol 190:987–996

    Google Scholar 

  • Coyne RS, Siebrecht M, Peitsch MC, Casanova JE (1994) Mutational analysis of polymeric immunoglobulin receptor/ligand interactions. Evidence for the involvement of multiple complementarity determining region (CDR)-like loops in receptor domain I. J Biol Chem 269:31620–31625

    CAS  PubMed  Google Scholar 

  • Danilova N, Bussmann J, Jekosch K, Steiner LA (2005) The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z. Nat Immunol 6:295–302

    Article  CAS  PubMed  Google Scholar 

  • Davis RS (2007) Fc receptor-like molecules. Annu Rev Immunol 25:525–560

    Article  CAS  PubMed  Google Scholar 

  • Ehrhardt GR, Cooper MD (2011) Immunoregulatory roles for fc receptor-like molecules. Curr Top Microbiol Immunol 350:89–104

    CAS  PubMed  Google Scholar 

  • Estevez O, Garet E, Olivieri D, Gambon-Deza F (2016) Amphibians have immunoglobulins similar to ancestral IgD and IgA from Amniotes. Mol Immunol 69:52–61

    Article  CAS  PubMed  Google Scholar 

  • Fayngerts SA, Najakshin AM, Taranin AV (2007) Species-specific evolution of the FcR family in endothermic vertebrates. Immunogenetics 59:493–506

    Article  CAS  PubMed  Google Scholar 

  • Ferkol T, Perales JC, Eckman E, Kaetzel CS, Hanson RW, Davis PB (1995) Gene transfer into the airway epithelium of animals by targeting the polymeric immunoglobulin receptor. J Clin Invest 95:493–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Getahun A, Lundqvist M, Middleton D, Warr G, Pilstrom L (1999) Influence of the mu-chain C-terminal sequence on polymerization of immunoglobulin M. Immunology 97:408–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goshima M, Sekiguchi R, Matsushita M, Nonaka M (2016) The complement system of elasmobranches revealed by liver transcriptome analysis of a hammerhead shark, Sphyrna zygaena. Dev Comp Immunol 61:13–24

    Article  CAS  PubMed  Google Scholar 

  • Guselnikov SV, Ramanayake T, Erilova AY, Mechetina LV, Najakshin AM, Robert J, Taranin AV (2008) The Xenopus FcR family demonstrates continually high diversification of paired receptors in vertebrate evolution. BMC Evol Biol 8:148

    Article  PubMed  PubMed Central  Google Scholar 

  • Hamburger AE, West AP, Bjorkman PJ (2004) Crystal structure of a polymeric immunoglobulin binding fragment of the human polymeric immunoglobulin receptor. Structure 12:1925–1935

    Google Scholar 

  • Hansen JD, Landis ED, Phillips RB (2005) Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish. Proc Natl Acad Sci U S A 102:6919–6924

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hirano M, Das S, Guo P, Cooper MD (2011) The evolution of adaptive immunity in vertebrates. Adv Immunol 109:125–157

    Article  CAS  PubMed  Google Scholar 

  • Honda S, Kurita N, Miyamoto A, Cho Y, Usui K, Takeshita K, Takahashi S, Yasui T, Kikutani H, Kinoshita T, Fujita T, Tahara-Hanaoka S, Shibuya K, Shibuya A (2009) Enhanced humoral immune responses against T-independent antigens in Fc alpha/muR-deficient mice. Proc Natl Acad Sci U S A 106:11230–11235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Honjo K, Kubagawa Y, Jones DM, Dizon B, Zhu Z, Ohno H, Izui S, Kearney JF, Kubagawa H (2012) Altered Ig levels and antibody responses in mice deficient for the Fc receptor for IgM (FcμR). Proc Natl Acad Sci U S A 109:15882–15887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Honjo K, Kubagawa Y, Kearney JF, Kubagawa H (2015) Unique ligand-binding property of the human IgM Fc receptor. J Immunol 194:1975–1982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Honjo K, Kubagawa Y, Suzuki Y, Takagi M, Ohno H, Bucy RP, Izui S, Kubagawa H (2014) Enhanced auto-antibody production and Mott cell formation in FcmuR-deficient autoimmune mice. Int Immunol 26:659–672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hunziker W, Whitney JA, Mellman I (1991) Selective inhibition of transcytosis by brefeldin A in MDCK cells. Cell 67:617–627

    Article  CAS  PubMed  Google Scholar 

  • International Chicken Genome Sequencing C (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432:695–716

    Google Scholar 

  • Kaetzel CS (2005) The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunol Rev 206:83–99

    Article  CAS  PubMed  Google Scholar 

  • Kaetzel CS (2014) Coevolution of mucosal immunoglobulins and the polymeric immunoglobulin receptor: Evidence that the commensal microbiota provided the driving force. ISRN Immunology, 1–20. doi:10.1155/2014/541537

    Google Scholar 

  • Kasahara M, Sutoh Y (2014) Two forms of adaptive immunity in vertebrates: similarities and differences. Adv Immunol 122:59–90

    Article  CAS  PubMed  Google Scholar 

  • Kikuno K, Kang DW, Tahara K, Torii I, Kubagawa HM, Ho KJ, Baudino L, Nishizaki N, Shibuya A, Kubagawa H (2007) Unusual biochemical features and follicular dendritic cell expression of human Fcα/μ receptor. Eur J Immunol 37:3540–3550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klimovich VB (2011) IgM and its receptors: structural and functional aspects. Biochemistry (Mosc) 76:534–549

    Article  CAS  Google Scholar 

  • Krajci P, Solberg R, Sandberg M, Oyen O, Jahnsen T, Brandtzaeg P (1989) Molecular cloning of the human transmembrane secretory component (poly-Ig receptor) and its mRNA expression in human tissues. Biochem Biophys Res Commun 158:783–789

    Article  CAS  PubMed  Google Scholar 

  • Kubagawa H, Oka S, Kubagawa Y, Torii I, Takayama E, Kang DW, Gartland GL, Bertoli LF, Mori H, Takatsu H, Kitamura T, Ohno H, Wang JY (2009) Identity of the elusive IgM Fc receptor (FcmuR) in humans. J Exp Med 206:2779–2793

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubagawa H, Oka S, Kubagawa Y, Torii I, Takayama E, Kang DW, Jones D, Nishida N, Miyawaki T, Bertoli LF, Sanders SK, Honjo K (2014) The long elusive IgM Fc receptor. FcmuR. J Clin Immunol 34(Suppl 1):S35–S45

    Article  PubMed  Google Scholar 

  • Lanier LL (2009) DAP10- and DAP12-associated receptors in innate immunity. Immunol Rev 227:150–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Letunic I, Doerks T, Bork P (2012) SMART 7: recent updates to the protein domain annotation resource. Nucleic Acids Res 40:D302–D305

    Article  CAS  PubMed  Google Scholar 

  • Magadan-Mompo S, Sanchez-Espinel C, Gambon-Deza F (2013a) IgH loci of American alligator and saltwater crocodile shed light on IgA evolution. Immunogenetics 65:531–541

    Article  CAS  PubMed  Google Scholar 

  • Magadan-Mompo S, Sanchez-Espinel C, Gambon-Deza F (2013b) Immunoglobulin genes of the turtles. Immunogenetics 65:227–237

    Article  CAS  PubMed  Google Scholar 

  • Nguyen XH, Lang PA, Lang KS, Adam D, Fattakhova G, Foger N, Kamal MA, Prilla P, Mathieu S, Wagner C, Mak T, Chan AC, Lee KH (2011) Toso regulates the balance between apoptotic and nonapoptotic death receptor signaling by facilitating RIP1 ubiquitination. Blood 118:598–608

    Article  CAS  PubMed  Google Scholar 

  • Nikolaidis N, Klein J, Nei M (2005) Origin and evolution of the Ig-like domains present in mammalian leukocyte receptors: insights from chicken, frog, and fish homologues. Immunogenetics 57:151–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Norderhaug IN, Johansen FE, Krajci P, Brandtzaeg P (1999) Domain deletions in the human polymeric Ig receptor disclose differences between its dimeric IgA and pentameric IgM interaction. Eur J Immunol 29:3401–3409

    Article  CAS  PubMed  Google Scholar 

  • Okamoto CT, Shia SP, Bird C, Mostov KE, Roth MG (1992) The cytoplasmic domain of the polymeric immunoglobulin receptor contains two internalization signals that are distinct from its basolateral sorting signal. J Biol Chem 267:9925–9932

    CAS  PubMed  Google Scholar 

  • Ouchida R, Mori H, Hase K, Takatsu H, Kurosaki T, Tokuhisa T, Ohno H, Wang JY (2012) Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses. Proc Natl Acad Sci U S A 109:E2699–E2706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pumphrey RS (1986) Computer models of the human immunoglobulins Binding sites and molecular interactions. Immunol Today 7:206–211

    Article  CAS  PubMed  Google Scholar 

  • Rodewald HR, Arulanandam AR, Koyasu S, Reinherz EL (1991) The high affinity Fc epsilon receptor gamma subunit (Fc epsilon RI gamma) facilitates T cell receptor expression and antigen/major histocompatibility complex-driven signaling in the absence of CD3 zeta and CD3 eta. J Biol Chem 266:15974–15978

    CAS  PubMed  Google Scholar 

  • Roe M, Norderhaug IN, Brandtzaeg P, Johansen FE (1999) Fine specificity of ligand-binding domain 1 in the polymeric Ig receptor: importance of the CDR2-containing region for IgM interaction. J Immunol 162:6046–6052

    CAS  PubMed  Google Scholar 

  • Saha NR, Ota T, Litman GW, Hansen J, Parra Z, Hsu E, Buonocore F, Canapa A, Cheng JF, Amemiya CT (2014) Genome complexity in the coelacanth is reflected in its adaptive immune system. J Exp Zool B Mol Dev Evol 322:438–463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sakamoto N, Shibuya K, Shimizu Y, Yotsumoto K, Miyabayashi T, Sakano S, Tsuji T, Nakayama E, Nakauchi H, Shibuya A (2001) A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non-hematopoietic tissues. Eur J Immunol 31:1310–1316

    Article  CAS  PubMed  Google Scholar 

  • Shibuya A, Sakamoto N, Shimizu Y, Shibuya K, Osawa M, Hiroyama T, Eyre HJ, Sutherland GR, Endo Y, Fujita T, Miyabayashi T, Sakano S, Tsuji T, Nakayama E, Phillips JH, Lanier LL, Nakauchi H (2000) Fc alpha/mu receptor mediates endocytosis of IgM-coated microbes. Nat Immunol 1:441–446

    Article  CAS  PubMed  Google Scholar 

  • Shima H, Takatsu H, Fukuda S, Ohmae M, Hase K, Kubagawa H, Wang JY, Ohno H (2010) Identification of TOSO/FAIM3 as an Fc receptor for IgM. Int Immunol 22:149–156

    Article  CAS  PubMed  Google Scholar 

  • Shimizu Y, Honda S, Yotsumoto K, Tahara-Hanaoka S, Eyre HJ, Sutherland GR, Endo Y, Shibuya K, Koyama A, Nakauchi H, Shibuya A (2001) Fc(α)/μ receptor is a single gene-family member closely related to polymeric immunoglobulin receptor encoded on Chromosome 1. Immunogenetics 53:709–711

    Article  CAS  PubMed  Google Scholar 

  • Sletten K, Christensen TB, Brandtzaeg P (1975) Human secretory component–III. Carbohydrates, amino acids and N-terminal sequence. Immunochemistry 12:783–785

    Article  CAS  PubMed  Google Scholar 

  • Stadtmueller BM, Huey-Tubman KE, Lopez CJ, Yang Z, Hubbell WL, Bjorkman PJ (2016) The structure and dynamics of secretory component and its interactions with polymeric immunoglobulins. Elife 5

    Google Scholar 

  • Sun Y, Wei Z, Li N, Zhao Y (2013) A comparative overview of immunoglobulin genes and the generation of their diversity in tetrapods. Dev Comp Immunol 39:103–109

    Article  PubMed  Google Scholar 

  • Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Viertlboeck BC, Gobel TW (2011) The chicken leukocyte receptor cluster. Vet Immunol Immunopathol 144:1–10

    Article  CAS  PubMed  Google Scholar 

  • Vire B, David A, Wiestner A (2011) TOSO, the Fcmicro receptor, is highly expressed on chronic lymphocytic leukemia B cells, internalizes upon IgM binding, shuttles to the lysosome, and is downregulated in response to TLR activation. J Immunol 187:4040–4050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang H, Coligan JE, Morse HC III (2016) Emerging functions of natural IgM and Its Fc receptor FCMR in immune homeostasis. Front Immunol 7:99

    Google Scholar 

  • Weissman AM, Hou D, Orloff DG, Modi WS, Seuanez H, O’Brien SJ, Klausner RD (1988) Molecular cloning and chromosomal localization of the human T-cell receptor zeta chain: distinction from the molecular CD3 complex. Proc Natl Acad Sci U S A 85:9709–9713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wieland WH, Orzaez D, Lammers A, Parmentier HK, Verstegen MW, Schots A (2004) A functional polymeric immunoglobulin receptor in chicken (Gallus gallus) indicates ancient role of secretory IgA in mucosal immunity. Biochem J 380:669–676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoo EM, Trinh KR, Lim H, Wims LA, Morrison SL (2011) Characterization of IgA and IgM binding and internalization by surface-expressed human Fcalpha/mu receptor. Mol Immunol 48:1818–1826

    Article  CAS  PubMed  Google Scholar 

  • Zhang YA, Salinas I, Li J, Parra D, Bjork S, Xu Z, Lapatra SE, Bartholomew J, Sunyer JO (2010) IgT, a primitive immunoglobulin class specialized in mucosal immunity. Nat Immunol 11:827–835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Y, Cui H, Whittington CM, Wei Z, Zhang X, Zhang Z, Yu L, Ren L, Hu X, Zhang Y, Hellman L, Belov K, Li N, Hammarstrom L (2009) Ornithorhynchus anatinus (platypus) links the evolution of immunoglobulin genes in eutherian mammals and nonmammalian tetrapods. J Immunol 183:3285–3293

    Article  CAS  PubMed  Google Scholar 

  • Zikan J, Bennett JC (1973) Isolation of F(c)5μ and Fabμ fragments of human IgM. Eur J Immunol 3:415–419

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was financially supported by a grant from the Swedish National Research Council VR-NT. We would also like to thank Dr. Michael Thorpe for linguistic revision of the manuscript.

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  1. Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Box 596, 751 24, Uppsala, Sweden

    Srinivas Akula & Lars Hellman

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Correspondence to Lars Hellman .

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  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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Akula, S., Hellman, L. (2017). The Appearance and Diversification of Receptors for IgM During Vertebrate Evolution. 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_22

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