{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T16:49:33Z","timestamp":1771001373890,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2005,11,29]],"date-time":"2005-11-29T00:00:00Z","timestamp":1133222400000},"content-version":"vor","delay-in-days":6695,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1987,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The association between the HLA\u2013DR4 histocompatibility antigen and in vitro synthesis of IgM and IgM rheumatoid factor (IgM\u2010RF) by blood mononuclear cells was investigated in 35 normal subjects. In vitro cultures of T and B cells were stimulated with pokeweed mitogen, and the secreted IgM\u2010RF, tetanus antibody, and total IgM protein were measured by solid\u2010phase radioimmunoassay. In cultures containing unseparated T cells, IgM\u2010RF production in the DR4+ and DR4\u2013subgroups was not significantly different. However, depletion of OKT8+ cells containing T suppressor cells resulted in significantly higher IgM and IgM\u2010RF synthesis in the DR4+ subgroup. Moreover, 6 of the 8 highest levels of IgM\u2010RF were produced by DR4+ individuals, while only 7 of the remaining 27 individuals were DR4+ (<jats:italic>P<\/jats:italic> = 0.035). Ratios of secreted IgM\u2010RF : IgM indicated that there was a relative enrichment for IgM\u2010RF\u2013specific B cell precursors in DR4+ high responders, although total numbers of circulating B cells were not increased. High responder B cells had high levels of responsiveness when mixed with T helper cells from low responders, whereas low responder B cells consistently produced low responses, even when cocultured with T helper cells from high responder donors. The data suggest that a subset of normal individuals has a pokeweed mitogen\u2013responsive lymphocyte population that contains a B cell subpopulation specific for IgM\u2010RF synthesis and that this condition is associated with HLA\u2013DR4. In certain individuals who have the DR4 type, there may be a component of a susceptible genetic background, upon which other factors act to induce IgM\u2010RF synthesis and which may produce clinical manifestations of rheumatoid arthritis.<\/jats:p>","DOI":"10.1002\/art.1780300801","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T22:02:16Z","timestamp":1171490536000},"page":"841-848","source":"Crossref","is-referenced-by-count":9,"title":["High levels of in vitro igm rheumatoid factor synthesis correlate with hla\u2013dr4 in normal individuals"],"prefix":"10.1002","volume":"30","author":[{"given":"Nancy J.","family":"Olsen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Stastny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo E.","family":"Jasin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,11,29]]},"reference":[{"key":"e_1_2_1_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108382"},{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197804202981602"},{"key":"e_1_2_1_3_2","first-page":"681","volume-title":"Rheumatoid arthritis, Histocompatibility Testing 1980","author":"Stastny P","year":"1980"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780230307"},{"key":"e_1_2_1_5_2","first-page":"370","article-title":"HLA\u2010DR4 antigen and IgM rheumatoid factors","volume":"9","author":"Viana Queiros M","year":"1982","journal-title":"J Rheumatol"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108997"},{"key":"e_1_2_1_7_2","first-page":"314s","article-title":"Association between HLA haplotype and low responsiveness to schistosomal worm antigen in man","volume":"152","author":"Sasazuki T","year":"1980","journal-title":"J Exp Med (suppl)"},{"key":"e_1_2_1_8_2","first-page":"439","volume-title":"Immune response genes, Fundamental Immunology","author":"Paul WE","year":"1984"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.148.5.1429"},{"key":"e_1_2_1_10_2","doi-asserted-by":"crossref","first-page":"934","DOI":"10.4049\/jimmunol.125.2.934","article-title":"In vitro synthesis of IgM rheumatoid factor by lymphocytes from healthy adults","volume":"125","author":"Koopman WJ","year":"1980","journal-title":"J Immunol"},{"key":"e_1_2_1_11_2","first-page":"129","article-title":"Study of HLA antigens in ten multiple\u2010case rheumatoid arthritis families","volume":"11","author":"Nunez G","year":"1984","journal-title":"J Rheumatol"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00541247"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.6.2844"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270904"},{"key":"e_1_2_1_15_2","first-page":"1289","article-title":"Activation of human B lymphocytes. 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Characterization of multiple populations of naturally occurring immunoregulatory cells of polyclonally\u2010induced in vitro human B cell function","volume":"123","author":"Haynes BF","year":"1979","journal-title":"J Immunol"},{"key":"e_1_2_1_16_2","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.4049\/jimmunol.132.4.1779","article-title":"T cell regulation of polyclonally induced immunoglobulin cretion in humans","volume":"132","author":"Rosenkoetter M","year":"1984","journal-title":"J Immunol"},{"key":"e_1_2_1_17_2","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.4049\/jimmunol.131.5.2282","article-title":"Phenotype of accessory cell necessary for mitogen\u2010stimulated T cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L\u2010le methyl ester","volume":"131","author":"Thiele D","year":"1983","journal-title":"J Immunol"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.3109\/03009748309098541"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90004-8"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.157.2.530"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780250206"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0090-1229(83)90059-4"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198111193052102"}],"container-title":["Arthritis &amp; Rheumatism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.1780300801","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.1780300801","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:05:45Z","timestamp":1700737545000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/art.1780300801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1987,8]]},"references-count":23,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1987,8]]}},"alternative-id":["10.1002\/art.1780300801"],"URL":"https:\/\/doi.org\/10.1002\/art.1780300801","archive":["Portico"],"relation":{},"ISSN":["0004-3591","1529-0131"],"issn-type":[{"value":"0004-3591","type":"print"},{"value":"1529-0131","type":"electronic"}],"subject":[],"published":{"date-parts":[[1987,8]]}}}