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Amphibians Polymeric Ig Receptor From Secretory Antibody Formation: Conserved Binding Interactions between J Chain and Polymeric Ig Receptor from Humans and Amphibians This information is current as of September 29, 2021. Ranveig Braathen, Valerie S. Hohman, Per Brandtzaeg and Finn-Eirik Johansen J Immunol 2007; 178:1589-1597; ; doi: 10.4049/jimmunol.178.3.1589 http://www.jimmunol.org/content/178/3/1589 Downloaded from References This article cites 48 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/178/3/1589.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 29, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2007 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Secretory Antibody Formation: Conserved Binding Interactions between J Chain and Polymeric Ig Receptor from Humans and Amphibians1 Ranveig Braathen,* Valerie S. Hohman,† Per Brandtzaeg,* and Finn-Eirik Johansen2* Abs of the secretory Ig (SIg) system reinforce numerous innate defense mechanisms to protect the mucosal surfaces against microbial penetration. SIgs are generated by a unique cooperation between two distinct cell types: plasma cells that produce polymers of IgA or IgM (collectively called pIgs) and polymeric Ig receptor (pIgR)-expressing secretory epithelial cells that mediate export of the pIgs to the lumen. Apical delivery of SIgs occurs by cleavage of the pIgR to release its extracellular part as a pIg-bound secretory component, whereas free secretory components are derived from an unoccupied receptor. The joining chain (J chain) is crucial in pIg/SIg formation because it serves to polymerize Igs and endows them with a binding site for the pIgR. In Downloaded from this study, we show that the J chain from divergent tetrapods including mammals, birds, and amphibians efficiently induced polymerization of human IgA, whereas the J chain from nurse shark (a lower vertebrate) did not. Correctly assembled polymers showed high affinity to human pIgR. Sequence analysis of the J chain identified two regions, conserved only in tetrapods, which by mutational analysis were found essential for pIgA-pIgR complexing. Furthermore, we isolated and characterized pIgR from the amphibian Xenopus laevis and demonstrated that its pIg binding domain showed high affinity to human pIgA. These results showed that the functional site of interaction between pIgR, J chain and Ig H chains is conserved in these species and suggests that http://www.jimmunol.org/ SIgs originated in an ancestor common to tetrapods. The Journal of Immunology, 2007, 178: 1589–1597. ecretory IgA (SIgA)3 has been recognized as the major Ab with innate defense mechanisms on the mucosal surfaces to pro- class in mammals for Ͼ40 years. The conventional expla- vide protection against pathogens and to restrict commensals to the S nation for this huge SIgA production has been that it must lumen (5–7). protect the large mucosal surfaces against a many different bacte- Plasma cells located in the mucosal lamina propria of the gas- rial and viral pathogens. Recently, however, the role of SIgA in trointestinal and respiratory tracts are preferentially switched to host interactions with the commensal bacteria in the intestine has IgA and coexpress the joining chain (J chain). Therefore, mucosal been revealed (1). Thus SIgA is important both for defense against plasma cells secrete mostly polymeric IgA (pIgA; predominantly by guest on September 29, 2021 mucosal pathogens but also to restrict the indigenous gut flora to dimers) with the capacity to bind to the polymeric Ig receptor the lumen. (pIgR) (8, 9). SIgA production is initiated when pIgA binds pIgR Animals are adapted to live with vast number of bacteria colo- expressed on the basolateral side of epithelial cells lining the mu- nizing their mucosal surfaces. Such mutualistic microorganisms cosal surfaces. Endocytosis and intracellular trafficking of the re- provide benefit to the host, not only as competitors of pathogenic ceptor-ligand complex to the apical plasma membrane is mediated bacteria but also through direct positive tissue interactions (2, 3). by sorting signals in the cytoplasmic tail of the pIgR, and lumenal However, if the mucosal barrier is breached the indigenous micro- delivery of SIgA occurs by cleavage of the receptor near the biota may cause life-threatening infections or a severe tissue-dam- plasma membrane (10). Covalently bound secretory component aging response from the systemic immune system. In mammals, (SC; the extracellular cleaved piece of the pIgR) confers muco- luminal bacteria induce production of IgA Abs (4) that cooperate philic properties and proteolytic resistance to the SIgA molecule (11). Similarly generated SIgM Abs are mainly important in the neonate and in individuals with selective IgA deficiency (12), *Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathol- whereas constitutive transcytosis of unoccupied pIgR leads to the ogy, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Nor- secretion of free SC (12). † way; and Department of Biology, University of San Diego, San Diego, CA 92110 The J chain has been characterized in a range of species includ- Received for publication September 22, 2006. Accepted for publication November ing mammals (human (13, 14), mouse (15), bovine (16), rabbit 16, 2006. (17), and brushtail possum (18)), birds (chicken (19)), reptiles (tur- The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance tle (20)), amphibians (Xenopus laevis (21) and Rana catesbeiana with 18 U.S.C. Section 1734 solely to indicate this fact. (22)), and cartilaginous fish (nurse shark (23) and clearnose skate 1 Funding for this project has been provided by the Research Council of Norway. (24)). In humans, this unique 15-kD polypeptide contains eight 2 Address correspondence and reprint requests to Dr. Finn-Eirik Johansen, Laboratory Cys residues that form three intrachain bridges and two bridges to for Immunohistochemistry and Immunopathology, Institute of Pathology, University the tailpieces of IgA or IgM in human pIgs (25). No crystal struc- of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway. E-mail address: [email protected] ture is available for SIgA or SIgM, but several lines of evidence 3 Abbreviations used in this paper: SIgA, secretory IgA; CHO, Chinese hamster suggest that J chain and pIgR interact directly, although this re- ovary; D1, domain 1; D2, domain 2; J chain, joining chain; NIP, -iodo-4-hydroxy- mains controversial (8, 9, 25, 26). 2-nitrophenylacetyl; pIgA, polymeric IgA; pIgR, polymeric Ig receptor; SC, secretory Monomeric IgA (composed of two H chains and two L chains) component. readily form polymers when coexpressed with a J chain (13). Ear- Copyright © 2007 by The American Association of Immunologists, Inc. 0022-1767/07/$2.00 lier investigations into the function of the J chain showed that www.jimmunol.org 1590 CONSERVATION OF SECRETORY ANTIBODY FORMATION IN TETRAPODS Table I. Characteristics of J chain variants used in this study J-chain variant Sequencea Polymersb J Chainc Mock 16 Human 65 100 Ϯ 9 Mouse 51 Chicken 41 Xenopus 50 Bullfrog 16 Nurse shark 19 Region 1 wild type 25-SSEDPNED-32 65 100 Ϯ 9 SSE25AAA AAADPNED 80 124 Ϯ 20 ED27AA SSAAPNED 67 124 Ϯ 4 DP28AA SSEAANED 64 107 Ϯ 5 NED30AAA SSEDPAAA 67 88 Ϯ 5 Region 2 wild type 45-NNRENISDPTS-55 65 100 Ϯ 9 NN45AA AARENISDPTS 75 115 Ϯ 13 RE47AA NNAANISDPTS 81 103 Ϯ 2 ISD50AAA NNRENAAAPTS 55 100 Ϯ 10 TS54AA NNRENISDPAA 62 122 Ϯ 10 N49A NNREAISDPTS 46 140 Ϯ 6 ISD50ASA NNRENASAPTS 72 107 Ϯ 9 Downloaded from Region 3 wild type 102-YTYDRNK-108 65 100 Ϯ 9 YTY102AAA AAADRNK 70 116 Ϯ 7 RNK106AAA YTYDAAA 68 103 Ϯ 3 YTY102FTF FTFDRNK 70 100 Ϯ 3 T103A YAYDRNK 58 55 Ϯ 8 D105A YTYARNK 84 110 Ϯ 12 R106A YTYDANK 73 111 Ϯ 14 http://www.jimmunol.org/ N107A YTYDRAK 89 119 Ϯ 19 K108A YTYDRNA 67 77 Ϯ 2 D105R YTYRRNK 87 83 Ϯ 3 R106E YTYDENK 44 66 Ϯ 2 DR105RE YTYRENK 73 91 Ϯ 7 a Amino acid letters in bold font represent a substitution. b The amount of polymer secreted by CHO cells cotransfected with IgA and the indicated J chain calculated as a percentage of total IgA as described in Materials and Methods. c J chain content was determined by ELISA as described in Materials and Methods. J chain content in the polymeric IgA fraction co-expressed with wild-type human IgA was set to 100%. by guest on September 29, 2021 structural requirements for polymerization of IgA were less strin- amino acid sequence of the extracellular domain 1 (D1) of human or gent than the requirements for pIgR/SC binding of the resulting chicken pIgR as the query both identified an expressed sequence tag pu- polymers (27). In this study we show that J chain from several tatively encoding X. laevis pIgR. The clone (IMAGE 4031968) was ob- tained from Geneservice and sequenced in full (GenBank accession no. different tetrapod species is capable of inducing polymerization of EF079076). An expression plasmid for xD1-hD2D5 SC was constructed by human IgA and that the resulting pIgA binds human pIgR/SC.
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