{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:26:22Z","timestamp":1760264782641},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2004,8,5]],"date-time":"2004-08-05T00:00:00Z","timestamp":1091664000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To understand in detail the mechanisms of autoantibody production in patients with systemic lupus erythematosus (SLE), we performed a comprehensive analysis of the normal human immunoglobulin light chain V<jats:sub>\u03bb<\/jats:sub> repertoire and compared it with the V<jats:sub>\u03bb<\/jats:sub> repertoire in SLE patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The SLE V<jats:sub>\u03bb<\/jats:sub> repertoire of B cells obtained from 3 SLE patients was analyzed and compared in detail with the V<jats:sub>\u03bb<\/jats:sub> repertoire of IgM+ B cells obtained from 3 human fetal spleens and IgM+,CD5+ B cells obtained from 2 normal adults. Conventional IgM+,CD5\u2013 B cells obtained from normal adults were used as controls. V<jats:sub>\u03bb<\/jats:sub>\u2013J<jats:sub>\u03bb<\/jats:sub> rearrangements were amplified from the genomic DNA of individual B cells by polymerase chain reaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expressed V<jats:sub>\u03bb<\/jats:sub> repertoire of SLE patients contained several similarities with the expressed repertoire of the fetus and the adult CD5+ B cells. The V<jats:sub>\u03bb<\/jats:sub> genes 3L and 1G were overexpressed in the fetus, the adult CD5+ B cells, and the patients with SLE. The selection for rearrangements with restricted junctional diversity by utilization of homology\u2010mediated joining, together with diminished N nucleotide addition, was a prominent feature of fetal, adult CD5+, and SLE B cell repertoires. Furthermore, profound expansion of V<jats:sub>\u03bb<\/jats:sub> clones with identical third complementarity\u2010determining regions was observed in the adult CD5+, fetal, and SLE B cell repertoires. Notably, significant numbers of expanded adult CD5+ B cells, fetal, and SLE V<jats:sub>\u03bb<\/jats:sub> clones utilized homology\u2010mediated joining at the V<jats:sub>\u03bb<\/jats:sub>\u2013J<jats:sub>\u03bb<\/jats:sub> junctions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These data demonstrate that the SLE V<jats:sub>\u03bb<\/jats:sub>\u2013J<jats:sub>\u03bb<\/jats:sub> repertoire manifests characteristics of normal adult IgM+,CD5+ and fetal B cell populations that are known to be enriched for the production of natural autoantibodies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.20439","type":"journal-article","created":{"date-parts":[[2004,8,9]],"date-time":"2004-08-09T20:08:20Z","timestamp":1092082100000},"page":"2604-2614","source":"Crossref","is-referenced-by-count":14,"title":["The V<sub>\u03bb<\/sub>\u2013J<sub>\u03bb<\/sub> repertoire of patients with systemic lupus erythematosus manifests characteristics of the natural antibody repertoire"],"prefix":"10.1002","volume":"50","author":[{"given":"Jisoo","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Joo","family":"Cho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter E.","family":"Lipsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,8,5]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60641-0"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81108-3"},{"key":"e_1_2_5_4_2","first-page":"335","article-title":"Reactivity of mouse antibodies against bromalain\u2010treated mouse erythrocytes with thrombin\u2010treated mouse platelets","volume":"66","author":"Kawaguchi S","year":"1989","journal-title":"Immunol"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2000.imr017515.x"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8472"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.24.11550"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.134.2.765"},{"key":"e_1_2_5_9_2","doi-asserted-by":"crossref","first-page":"3643","DOI":"10.4049\/jimmunol.142.10.3643","article-title":"A single VH gene is utilized predominantly in anti\u2010BrMRBC hybridomas derived from purified Ly\u20101 B cells: definition of the VH11 family","volume":"142","author":"Hardy RR","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_5_10_2","doi-asserted-by":"crossref","first-page":"4054","DOI":"10.4049\/jimmunol.142.11.4054","article-title":"Nucleotide sequences of eight human natural autoantibody VH regions reveal apparent restricted use of VH families","volume":"142","author":"Sanz I","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.885"},{"key":"e_1_2_5_12_2","doi-asserted-by":"crossref","first-page":"5988","DOI":"10.4049\/jimmunol.152.12.5988","article-title":"Structure\u2010function studies on a polyreactive (natural) autoantibody: polyreactivity is dependent on somatically generated sequences in the third complementarity\u2010determining region of the antibody heavy chain","volume":"152","author":"Martin T","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830220709"},{"key":"e_1_2_5_14_2","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.4049\/jimmunol.149.6.2234","article-title":"A human systemic lupus erythematosus related anti\u2010cardiolipin\/single stranded DNA autoantibody is encoded by a somatically mutated variant of the developmentally restricted 51pl VH gene","volume":"149","author":"Van Es JH","year":"1992","journal-title":"J Immunol"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(98)00095-9"},{"key":"e_1_2_5_16_2","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.4049\/jimmunol.156.8.3065","article-title":"Structural elements controlling anti\u2010DNA antibody affinity and their relationship to anti\u2010phosphorylcholine activity","volume":"156","author":"Pewzner\u2010Jung Y","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_5_17_2","doi-asserted-by":"crossref","first-page":"190","DOI":"10.4049\/jimmunol.155.1.190","article-title":"Analysis of the heavy chain repertoire of human peripheral B cells using single cell polymerase chain reaction","volume":"155","author":"Brezinschek HP","year":"1995","journal-title":"J Immunol"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6322"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780400928"},{"key":"e_1_2_5_20_2","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.4049\/jimmunol.162.4.2137","article-title":"Molecular mechanism and selection influence in the generation of human V\u03bbJ\u03bb repertoire","volume":"162","author":"Farner NL","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_5_21_2","volume-title":"V BASE sequence directory","author":"Tomlinson IM","year":"1996"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/337562a0"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/342385a0"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.4.999"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.4.1009"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.1993.tb00753.x"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(89)90268-5"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1995.tb55882.x"},{"key":"e_1_2_5_29_2","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.4049\/jimmunol.149.11.3588","article-title":"The anti\u2010DNA\u2010associated idiotype 8.12 is encoded by the V\u03bbII gene family and maps to the vicinity of L chain CDR1","volume":"149","author":"Paul E","year":"1992","journal-title":"J Immunol"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117164"},{"key":"e_1_2_5_31_2","doi-asserted-by":"crossref","first-page":"685","DOI":"10.4049\/jimmunol.143.2.685","article-title":"Analysis of variable region genes encoding a human anti\u2010DNA antibody of normal origin","volume":"143","author":"Cairns E","year":"1989","journal-title":"J Immunol"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/clim.1999.4740"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar329"},{"key":"e_1_2_5_34_2","doi-asserted-by":"crossref","first-page":"6060","DOI":"10.4049\/jimmunol.162.10.6060","article-title":"IgM heavy chain complementarity\u2010determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth","volume":"162","author":"Shiokawa S","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.172.5.1377"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1990.tb07382.x"},{"key":"e_1_2_5_37_2","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.4049\/jimmunol.163.2.1027","article-title":"Immunoglobulin \u03bb and heavy chain gene usage in early untreated systemic lupus erythematosus suggests intensive B cell stimulation","volume":"163","author":"Dorner T","year":"1999","journal-title":"J Immunol"},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2237433"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/2.7.639"},{"key":"e_1_2_5_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.1.222"},{"key":"e_1_2_5_41_2","doi-asserted-by":"crossref","first-page":"4343","DOI":"10.4049\/jimmunol.147.12.4343","article-title":"Predominance of the prototypic T15 anti\u2010phosphorylcholine junctional sequence in neonatal pre\u2010B cells","volume":"147","author":"Feeney AJ","year":"1991","journal-title":"J Immunol"},{"key":"e_1_2_5_42_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/11.22.7887"},{"key":"e_1_2_5_43_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.2.329"},{"key":"e_1_2_5_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.169.5.1631"},{"key":"e_1_2_5_45_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.3.525"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.20439","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.20439","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T23:37:51Z","timestamp":1696981071000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.20439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8]]},"references-count":44,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2004,8]]}},"alternative-id":["10.1002\/art.20439"],"URL":"https:\/\/doi.org\/10.1002\/art.20439","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,8]]}}}