{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T07:44:25Z","timestamp":1764402265438},"reference-count":84,"publisher":"Rockefeller University Press","issue":"8","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,10,16]]},"abstract":"<jats:p>Mature B cells can alter their antibody repertoires by several mechanisms, including immunoglobulin heavy chain variable region (VH) replacement. This process changes the antigen combining site by replacing a portion of the original VH\/diversity\/heavy chain joining region (VHDJH) rearrangement with a corresponding portion of a new VH segment. This exchange can involve cryptic heptamer-like sequences embedded in the coding regions of VH genes.<\/jats:p>\n               <jats:p>While studying the B lymphocytes that expand in the synovial tissues of patients with rheumatoid arthritis (RA), clones with VHDJH variants that were apparently generated by VH replacement were identified with surprising frequency (\u223c8%). Examples of multiple independent VH replacement events occurring in distinct progeny clones were also identified. These secondary VH rearrangements were documented at both the cDNA and genomic DNA levels and involved several heptamer-like sequences at four distinct locations within VH (three sites in framework region 3 and one in complementarity determining region 2). The identification of blunt-ended double-stranded DNA breaks at the embedded heptamers and the demonstration of recombinase activating gene (RAG) expression suggested that these rearrangements could occur in the synovial tissues, presumably in pseudo-germinal centers, and that they could be mediated by RAG in a recognition signal sequence\u2013specific manner. The presence of VH mutations in the clones that had undergone replacement indicated that these B cells were immunocompetent and could receive and respond to diversification signals. A relationship between these secondary VH gene rearrangements and the autoimmunity characteristic of RA should be considered.<\/jats:p>","DOI":"10.1084\/jem.192.8.1151","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:33Z","timestamp":1027702113000},"page":"1151-1164","update-policy":"http:\/\/dx.doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":77,"title":["Immunoglobulin Heavy Chain Variable Region Gene Replacement as a Mechanism for Receptor Revision in Rheumatoid Arthritis Synovial Tissue B Lymphocytes"],"prefix":"10.1084","volume":"192","author":[{"given":"Kenji","family":"Itoh","sequence":"first","affiliation":[{"name":"aDepartment of Medicine and the Department of Surgery, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Meffre","sequence":"additional","affiliation":[{"name":"cThe Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilia","family":"Albesiano","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine and the Department of Surgery, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Farber","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine and the Department of Surgery, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Dines","sequence":"additional","affiliation":[{"name":"bDepartment of Surgery, Long Island Jewish Medical Center, and the Department of Surgery, Albert Einstein College of Medicine, New Hyde Park, New York 11040"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Stein","sequence":"additional","affiliation":[{"name":"bDepartment of Surgery, Long Island Jewish Medical Center, and the Department of Surgery, Albert Einstein College of Medicine, New Hyde Park, New York 11040"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanley E.","family":"Asnis","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine and the Department of Surgery, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Furie","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine and the Department of Surgery, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita I.","family":"Jain","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine and the Department of Surgery, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Chiorazzi","sequence":"additional","affiliation":[{"name":"aDepartment of Medicine and the Department of Surgery, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2000,10,16]]},"reference":[{"key":"2023072509331426500_R1","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/302575a0","article-title":"Somatic generation of antibody diversity","volume":"302","author":"Tonegawa","year":"1983","journal-title":"Nature."},{"key":"2023072509331426500_R2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/0167-5699(92)90043-7","article-title":"VDJ recombination","volume":"13","author":"Alt","year":"1992","journal-title":"Immunol. Today."},{"key":"2023072509331426500_R3","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/0092-8674(80)90089-6","article-title":"An immunoglobulin heavy chain variable region gene is generated from three segments of DNAVH, D and JH","volume":"19","author":"Early","year":"1980","journal-title":"Cell."},{"key":"2023072509331426500_R4","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/286676a0","article-title":"Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes","volume":"286","author":"Sakano","year":"1980","journal-title":"Nature."},{"key":"2023072509331426500_R5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0065-2776(08)60886-X","article-title":"Recent advances in understanding V(D)J recombination","volume":"64","author":"Gellert","year":"1997","journal-title":"Adv. Immunol."},{"key":"2023072509331426500_R6","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1084\/jem.177.4.999","article-title":"Receptor editingan approach by autoreactive B cells to escape tolerance","volume":"177","author":"Gay","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R7","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1084\/jem.177.4.1165","article-title":"B lymphocytes may escape tolerance by revising their antigen receptors","volume":"177","author":"Radic","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R8","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1084\/jem.177.4.1009","article-title":"Receptor editing in self-reactive bone marrow B cells","volume":"177","author":"Tiegs","year":"1993","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R9","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/1074-7613(95)90064-0","article-title":"Immunoglobulin heavy chain gene replacementa mechanism of receptor editing","volume":"3","author":"Chen","year":"1995","journal-title":"Immunity."},{"key":"2023072509331426500_R10","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1002\/(SICI)1521-4141(199810)28:10<3362::AID-IMMU3362>3.0.CO;2-8","article-title":"V(H) gene replacement occurs in the spleen and bone marrow of non-autoimmune quasi-monoclonal mice","volume":"28","author":"Bertrand","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"2023072509331426500_R11","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1084\/jem.190.5.691","article-title":"Somatic mutation and light chain rearrangement generate autoimmunity in anti\u2013single-stranded DNA transgenic MRL\/lpr mice","volume":"190","author":"Brard","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R12","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1006\/jmbi.1998.2396","article-title":"Analysis of heavy and light chain pairings indicates that receptor editing shapes the human antibody repertoire","volume":"285","author":"de Wildt","year":"1999","journal-title":"J. Mol. Biol."},{"key":"2023072509331426500_R13","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1084\/jem.189.11.1791","article-title":"Secondary rearrangements and hypermutation generate sufficient B cell diversity to mount protective antiviral immunoglobulin responses","volume":"189","author":"Lopez-Macias","year":"1999","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S1074-7613(00)80675-5","article-title":"Life and death in germinal centers (redux)","volume":"4","author":"Kelsoe","year":"1996","journal-title":"Immunity."},{"key":"2023072509331426500_R15","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1600-065X.1998.tb01437.x","article-title":"Amino acid insertions and deletions contribute to diversify the human Ig repertoire","volume":"162","author":"Wilson","year":"1998","journal-title":"Immunol. Rev."},{"key":"2023072509331426500_R16","doi-asserted-by":"crossref","first-page":"2463","DOI":"10.1073\/pnas.95.5.2463","article-title":"Frequent occurrence of deletions and duplications during somatic hypermutationimplications for oncogene translocations and heavy chain disease","volume":"95","author":"Goossens","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072509331426500_R17","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1084\/jem.191.11.1813","article-title":"Revising B cell receptors","volume":"191","author":"Nemazee","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R18","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1084\/jem.191.11.1881","article-title":"Receptor revision of immunoglobulin heavy chain variable region genes in normal human B lymphocytes","volume":"191","author":"Wilson","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R19","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1056\/NEJM199005033221805","article-title":"Rheumatoid arthritis. Pathophysiology and implications for therapy","volume":"322","author":"Harris","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"2023072509331426500_R20","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0092-8674(00)81109-5","article-title":"Rheumatoid arthritis","volume":"85","author":"Feldmann","year":"1996","journal-title":"Cell."},{"key":"2023072509331426500_R21","first-page":"343","article-title":"The simultaneous occurrence of rheumatoid arthritis and agammaglobulinemia","volume":"49","author":"Good","year":"1957","journal-title":"J. Lab. Clin. Med."},{"key":"2023072509331426500_R22","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/j.1749-6632.1969.tb43107.x","article-title":"Experimental arthritis in man and rabbit dependent upon serum anti-immunoglobulin factors","volume":"168","author":"Rawson","year":"1969","journal-title":"Ann. NY Acad. Sci."},{"key":"2023072509331426500_R23","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1111\/j.1600-065X.1995.tb00067.x","article-title":"Chronicity of tissue-specific experimental autoimmune diseasea role for B cells?","volume":"144","author":"Holmdahl","year":"1995","journal-title":"Immunol. Rev."},{"key":"2023072509331426500_R24","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.4049\/jimmunol.155.4.2067","article-title":"Mice with the xid B cell defect are less susceptible to developing Staphylococcus aureus-induced arthritis","volume":"155","author":"Zhao","year":"1995","journal-title":"J. Immunol."},{"key":"2023072509331426500_R25","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1002\/eji.1830250321","article-title":"The role of the B cells in the adoptive transfer of collagen-induced arthritis from DBA\/1 (H-2q) to SCID (H-2d) mice","volume":"25","author":"Taylor","year":"1995","journal-title":"Eur. J. Immunol."},{"key":"2023072509331426500_R26","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/j.1699-0463.1940.tb01475.x","article-title":"On the occurrence of a factor in human serum activating the specific agglutination of sheep blood corpuscles","volume":"17","author":"Waaler","year":"1940","journal-title":"Acta Pathol. Microbiol. Scand."},{"key":"2023072509331426500_R27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3181\/00379727-68-16375","article-title":"Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis","volume":"68","author":"Rose","year":"1948","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"2023072509331426500_R28","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1093\/rheumatology\/33.4.336","article-title":"The prevalence of serum IgG antibodies to type II collagen in American patients with rheumatoid arthritis","volume":"33","author":"Clague","year":"1994","journal-title":"Br. J. Rheumatol."},{"key":"2023072509331426500_R29","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/1529-0131(199707)40:7<1210::AID-ART4>3.0.CO;2-T","article-title":"T cell responses to human type II collagen in patients with rheumatoid arthritis and healthy controls","volume":"40","author":"Snowden","year":"1997","journal-title":"Arthritis Rheum."},{"key":"2023072509331426500_R30","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1172\/JCI1316","article-title":"Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies","volume":"101","author":"Schellekens","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2023072509331426500_R31","first-page":"87","article-title":"Evidence implicating infectious agents in rheumatoid arthritis and juvenile rheumatoid arthritis","volume":"6","author":"Phillips","year":"1988","journal-title":"Clin. Exp. Rheumatol."},{"key":"2023072509331426500_R32","first-page":"1442","article-title":"Antibodies to synthetic peptides from Epstein-Barr nuclear antigen-1 in sera of patients with early rheumatoid arthritis and in preillness sera","volume":"17","author":"Kouri","year":"1990","journal-title":"J. Rheumatol."},{"key":"2023072509331426500_R33","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1136\/ard.53.2.137","article-title":"Influence of previous exposure to human parvovirus B19 infection in explaining susceptibility to rheumatoid arthritisan analysis of disease discordant twin pairs","volume":"53","author":"Hajeer","year":"1994","journal-title":"Ann. Rheum. Dis."},{"key":"2023072509331426500_R34","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0092-8674(00)81989-3","article-title":"Organ-specific disease provoked by systemic autoimmunity","volume":"87","author":"Kouskoff","year":"1996","journal-title":"Cell."},{"key":"2023072509331426500_R35","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S1074-7613(00)80045-X","article-title":"From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins","volume":"10","author":"Korganow","year":"1999","journal-title":"Immunity."},{"key":"2023072509331426500_R36","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1126\/science.286.5445.1732","article-title":"Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme","volume":"286","author":"Matsumoto","year":"1999","journal-title":"Science."},{"key":"2023072509331426500_R37","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1111\/j.1365-3083.1995.tb03596.x","article-title":"The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue","volume":"41","author":"Randen","year":"1995","journal-title":"Scand. J. Immunol."},{"key":"2023072509331426500_R38","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1073\/pnas.93.1.221","article-title":"Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis","volume":"93","author":"Schroder","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072509331426500_R39","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/322843a0","article-title":"Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma","volume":"322","author":"Kleinfield","year":"1986","journal-title":"Nature."},{"key":"2023072509331426500_R40","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1038\/322840a0","article-title":"A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production","volume":"322","author":"Reth","year":"1986","journal-title":"Nature."},{"key":"2023072509331426500_R41","doi-asserted-by":"crossref","first-page":"4475","DOI":"10.4049\/jimmunol.142.12.4475","article-title":"Analysis of VH gene replacement events in a B cell lymphoma","volume":"142","author":"Kleinfield","year":"1989","journal-title":"J. Immunol."},{"key":"2023072509331426500_R42","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1093\/intimm\/2.6.579","article-title":"VH to VHDJH rearrangement is mediated by the internal VH heptamer","volume":"2","author":"Covey","year":"1990","journal-title":"Int. Immunol."},{"key":"2023072509331426500_R43","doi-asserted-by":"crossref","first-page":"5795","DOI":"10.4049\/jimmunol.159.12.5795","article-title":"VH gene replacement in hyperselected B cells of the quasimonoclonal mouse","volume":"159","author":"Cascalho","year":"1997","journal-title":"J. Immunol."},{"key":"2023072509331426500_R44","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1093\/nar\/18.6.1652","article-title":"Immunoglobulin heavy chain gene rearrangement involving V-V region recombination","volume":"18","author":"Deane","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"2023072509331426500_R45","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1093\/intimm\/4.2.197","article-title":"Conserved patterns of somatic mutation and secondary VH gene rearrangement create aberrant Ig-encoding genes in Epstein-Barr virus-transformed and normal human B lymphocytes","volume":"4","author":"Brokaw","year":"1992","journal-title":"Int. Immunol."},{"key":"2023072509331426500_R46","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1182\/blood.V87.6.2506.bloodjournal8762506","article-title":"Clonal evolution in B-lineage acute lymphoblastic leukemia by contemporaneous VH-VH gene replacements and VH-DJH gene rearrangements","volume":"87","author":"Choi","year":"1996","journal-title":"Blood."},{"key":"2023072509331426500_R47","first-page":"S85","article-title":"Rheumatoid arthritis synovial B cells exhibit novel and unexpected features of the immunoglobulin V gene mutation process","volume":"42","author":"Itoh","year":"1999","journal-title":"Arthritis Rheum."},{"key":"2023072509331426500_R48","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum."},{"key":"2023072509331426500_R49","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1172\/JCI3009","article-title":"Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors","volume":"102","author":"Fais","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2023072509331426500_R50","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1172\/JCI118961","article-title":"Examples of in vivo isotype class switching in IgM+ chronic lymphocytic leukemia B cells","volume":"98","author":"Fais","year":"1996","journal-title":"J. Clin. Invest."},{"key":"2023072509331426500_R51","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1111\/j.1365-2141.1991.tb08570.x","article-title":"Immunoglobulin gene \u2018fingerprinting\u2019an approach to analysis of B lymphoid clonality in lymphoproliferative disorders","volume":"77","author":"Deane","year":"1991","journal-title":"Br. J. Haematol."},{"key":"2023072509331426500_R52","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/ar68","article-title":"Clonal expansion is a characteristic feature of the B-cell repertoire of patients with rheumatoid arthritis","volume":"2","author":"Itoh","year":"2000","journal-title":"Arthritis Res."},{"key":"2023072509331426500_R53","doi-asserted-by":"crossref","first-page":"6082","DOI":"10.1073\/pnas.85.16.6082","article-title":"Molecular characterization of T-cell antigen receptor expression by subsets of CD4\u2212 CD8\u2212 murine thymocytes","volume":"85","author":"Pearse","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072509331426500_R54","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1126\/science.278.5336.298","article-title":"V(D)J recombination in mature B cellsa mechanism for altering antibody responses","volume":"278","author":"Papavasiliou","year":"1997","journal-title":"Science."},{"key":"2023072509331426500_R55","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1101\/gad.7.12b.2520","article-title":"Double-strand signal sequence breaks in V(D)J recombination are blunt, 5\u2032-phosphorylated, RAG-dependent, and cell cycle regulated","volume":"7","author":"Schlissel","year":"1993","journal-title":"Genes Dev."},{"key":"2023072509331426500_R56","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1084\/jem.188.4.765","article-title":"Antigen receptor engagement turns off the V(D)J recombination machinery in human tonsil B cells","volume":"188","author":"Meffre","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R57","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/art.1780360509","article-title":"Analysis of immunoglobulin gamma heavy chain expression in synovial tissue of a patient with rheumatoid arthritis","volume":"36","author":"Bridges","year":"1993","journal-title":"Arthritis Rheum."},{"key":"2023072509331426500_R58","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/316412a0","article-title":"Molecular events during maturation of the immune response to oxazolone","volume":"316","author":"Berek","year":"1985","journal-title":"Nature."},{"key":"2023072509331426500_R59","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1111\/j.1749-6632.1995.tb55862.x","article-title":"Analysis of immunoglobulin gamma heavy chains from rheumatoid arthritis synovium. Evidence of antigen-driven selection","volume":"764","author":"Bridges","year":"1995","journal-title":"Ann. NY Acad. Sci."},{"key":"2023072509331426500_R60","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S1074-7613(00)80266-6","article-title":"Receptor editing, immune diversification, and self-tolerance","volume":"5","author":"Radic","year":"1996","journal-title":"Immunity."},{"key":"2023072509331426500_R61","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/j.1460-2075.1992.tb05093.x","article-title":"Immunoglobulin V gene replacement is caused by the intramolecular DNA deletion mechanism","volume":"11","author":"Usuda","year":"1992","journal-title":"EMBO (Eur. Mol. Biol. Organ.) J"},{"key":"2023072509331426500_R62","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1006\/clim.1999.4785","article-title":"Gene conversion events contribute to the polymorphic variation of the surrogate light chain gene lambda 5\/14.1","volume":"93","author":"Conley","year":"1999","journal-title":"Clin. Immunol."},{"key":"2023072509331426500_R63","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0092-8674(87)90189-9","article-title":"A hyperconversion mechanism generates the chicken light chain preimmune repertoire","volume":"48","author":"Reynaud","year":"1987","journal-title":"Cell."},{"key":"2023072509331426500_R64","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/0092-8674(87)90188-7","article-title":"Somatic diversification of the chicken immunoglobulin light chain gene is limited to the rearranged variable gene segment","volume":"48","author":"Thompson","year":"1987","journal-title":"Cell."},{"key":"2023072509331426500_R65","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/0092-8674(90)90502-6","article-title":"Somatic diversification of immunoglobulin heavy chain VDJ genesevidence for somatic gene conversion in rabbits","volume":"63","author":"Becker","year":"1990","journal-title":"Cel."},{"key":"2023072509331426500_R66","doi-asserted-by":"crossref","first-page":"3984","DOI":"10.4049\/jimmunol.162.7.3984","article-title":"Gene conversion and hypermutation during diversification of VH sequences in developing splenic germinal centers of immunized rabbits","volume":"162","author":"Schiaffella","year":"1999","journal-title":"J. Immunol."},{"key":"2023072509331426500_R67","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1101\/gad.3.7.1053","article-title":"V(D)J recombinationa functional definition of the joining signals","volume":"3","author":"Hesse","year":"1989","journal-title":"Genes Dev."},{"key":"2023072509331426500_R68","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S1074-7613(00)80508-7","article-title":"V(D)J recombination in Ku86-deficient micedistinct effects on coding, signal, and hybrid joint formation","volume":"7","author":"Bogue","year":"1997","journal-title":"Immunity."},{"key":"2023072509331426500_R69","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1128\/MCB.17.4.2226","article-title":"Ku86 is not required for protection of signal ends or for formation of nonstandard V(D)J recombination products","volume":"17","author":"Han","year":"1997","journal-title":"Mol. Cell. Biol."},{"key":"2023072509331426500_R70","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1172\/JCI119433","article-title":"Analysis of the human VH gene repertoire. Differential effects of selection and somatic hypermutation on human peripheral CD5+\/IgM+ and CD5\u2212\/IgM+ B cells","volume":"99","author":"Brezinschek","year":"1997","journal-title":"J. Clin. Invest."},{"key":"2023072509331426500_R71","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/eji.1830230233","article-title":"Biased usage of two restricted VH gene segments in VH replacement","volume":"23","author":"Komori","year":"1993","journal-title":"Eur. J. Immunol."},{"key":"2023072509331426500_R72","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1084\/jem.187.8.1169","article-title":"The normal counterpart of IgD myeloma cells in germinal center displays extensively mutated IgVH gene, Cmu-Cdelta switch, and lambda light chain expression","volume":"187","author":"Arpin","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072509331426500_R73","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1016\/S0092-8674(00)80373-6","article-title":"In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death","volume":"90","author":"Lam","year":"1997","journal-title":"Cell."},{"key":"2023072509331426500_R74","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/79739","article-title":"Circulating human B cells that express surrogate light chains and edited receptors","volume":"1","author":"Meffre","year":"2000","journal-title":"Nat. Immunol."},{"key":"2023072509331426500_R75","doi-asserted-by":"crossref","first-page":"3296","DOI":"10.4049\/jimmunol.148.10.3296","article-title":"Clonally related IgM rheumatoid factors undergo affinity maturation in the rheumatoid synovial tissue","volume":"148","author":"Randen","year":"1992","journal-title":"J. Immunol."},{"key":"2023072509331426500_R76","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF00541346","article-title":"Significance of rheumatoid factors in an eight-year longitudinal study on arthritis","volume":"8","author":"Tuomi","year":"1988","journal-title":"Rheumatol. Int."},{"key":"2023072509331426500_R77","first-page":"55","article-title":"Immunoglobulin classes, subclasses and complexes of IgG rheumatoid factor in rheumatoid plasma cells","volume":"12","author":"Munthe","year":"1972","journal-title":"Clin. Exp. Immunol."},{"key":"2023072509331426500_R78","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/28419","article-title":"V(D)J recombinase induction in splenic B lymphocytes is inhibited by antigen-receptor signalling","volume":"394","author":"Hertz","year":"1998","journal-title":"Nature."},{"key":"2023072509331426500_R79","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1172\/JCI3113","article-title":"Immunoglobulin kappa chain receptor editing in systemic lupus erythematosus","volume":"102","author":"Dorner","year":"1998","journal-title":"J. Clin. Invest."},{"key":"2023072509331426500_R80","first-page":"63","article-title":"Idiotypic and molecular characterization of human rheumatoid factors","volume":"48","author":"Chen","year":"1990","journal-title":"Chem. Immunol."},{"key":"2023072509331426500_R81","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/281605a0","article-title":"Evolutionary nucleotide replacements in DNA","volume":"281","author":"Jukes","year":"1979","journal-title":"Nature."},{"key":"2023072509331426500_R82","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/328805a0","article-title":"The role of clonal selection and somatic mutation in autoimmunity","volume":"328","author":"Shlomchik","year":"1987","journal-title":"Nature."},{"key":"2023072509331426500_R83","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0167-4781(95)00241-3","article-title":"Somatic hypermutagenesis in immunoglobulin genes. III. Somatic mutations in the chicken light chain locus","volume":"1306","author":"Rogozin","year":"1996","journal-title":"Biochim. Biophys. Acta."},{"key":"2023072509331426500_R84","doi-asserted-by":"crossref","first-page":"2538","DOI":"10.1172\/JCI119796","article-title":"Lupus-specific antibodies reveal an altered pattern of somatic mutation","volume":"100","author":"Manheimer-Lory","year":"1997","journal-title":"J. Clin. 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