{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T21:10:05Z","timestamp":1779916205971,"version":"3.53.1"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2004,10,8]],"date-time":"2004-10-08T00:00:00Z","timestamp":1097193600000},"content-version":"vor","delay-in-days":2441,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[1998,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multiple sclerosis (MS) cerebrospinal fluid and brain contain increased IgG and oligoclonal bands. Whether this oligoclonal and polyclonal IgG is directed against a disease\u2010relevant antigen remains unknown. To distinguish between random activation versus a targeted B\u2010cell response, we analyzed the IgG heavy chain variable region (V<jats:sub>H<\/jats:sub>) repertoire expressed in different lesions of an acute MS brain. To obtain a representative sample of the V<jats:sub>H<\/jats:sub> repertoire, we constructed directional complementary DNA libraries from plaque\u2010periplaque messenger RNA and amplified V<jats:sub>H<\/jats:sub> regions from the library by nested polymerase chain reaction. When MS V<jats:sub>H<\/jats:sub> sequences were aligned to germline segments, about 60% of different V<jats:sub>H<\/jats:sub> sequences in the acute MS brain were V<jats:sub>H<\/jats:sub>4 germline segments, significantly greater than the known approximately 20% V<jats:sub>H<\/jats:sub>4 germline prevalence. Specific V<jats:sub>H<\/jats:sub> sequences were overrepresented and expressed at multiple plaque sites. Within some overexpressed populations, there were distinct sequence differences (clonal variants) indicative of clonal expansion. Alignment of V<jats:sub>H<\/jats:sub> sequences to their closest germline counterparts revealed extensive somatic mutation and the preferential accumulation of amino acid replacement mutations in complementarity determining regions. These observations suggest the limited B\u2010cell response found in this acute MS brain was antigen driven.<\/jats:p>","DOI":"10.1002\/ana.410430214","type":"journal-article","created":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T15:12:24Z","timestamp":1104592344000},"page":"236-243","source":"Crossref","is-referenced-by-count":147,"title":["Restricted use of V<sub>H<\/sub>4 Germline segments in an acute multiple sclerosis brain"],"prefix":"10.1002","volume":"43","author":[{"given":"Gregory P.","family":"Owens","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Kannus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"Burgoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Smith\u2010Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Devlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald H.","family":"Gilden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,10,8]]},"reference":[{"key":"e_1_2_1_2_2","first-page":"337","volume-title":"Handbook of clinical neurology","author":"Reder AT","year":"1985"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.10.040192.001101"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/135245859600200404"},{"key":"e_1_2_1_5_2","volume-title":"Molecular cloning: a laboratory manual","author":"Maniatis T","year":"1982"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-162"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(88)90330-7"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-0934(97)00118-3"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(95)80166-9"},{"key":"e_1_2_1_10_2","doi-asserted-by":"crossref","first-page":"5290","DOI":"10.4049\/jimmunol.151.10.5290","article-title":"A majority of Ig H chain cDNA of normal human adult blood lymphocytes resembles cDNA for fetal Ig and natural autoantibodies","volume":"151","author":"Huang C","year":"1993","journal-title":"J Immunol"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.1.190"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1988.tb00763.x"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/381751a0"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/287335a0"},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(81)90191-X"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410060205"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(82)90018-2"},{"key":"e_1_2_1_18_2","first-page":"213","volume-title":"Handbook of clinical neurology","author":"Prineas JW","year":"1985"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830210419"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.2.409"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350103"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1996.0110"},{"key":"e_1_2_1_23_2","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.4049\/jimmunol.151.2.1051","article-title":"Autoanti\u2010red cell antibodies synthesized by patients with infectious mononucleosis utilize the VH4\u201021 gene segment","volume":"151","author":"Chapman CJ","year":"1993","journal-title":"J Immunol"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(82)90059-5"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.410430214","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.410430214","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T15:16:04Z","timestamp":1698506164000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.410430214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998,2]]},"references-count":23,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1998,2]]}},"alternative-id":["10.1002\/ana.410430214"],"URL":"https:\/\/doi.org\/10.1002\/ana.410430214","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[1998,2]]}}}