{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T01:40:16Z","timestamp":1700703616784},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,12,12]],"date-time":"2005-12-12T00:00:00Z","timestamp":1134345600000},"content-version":"vor","delay-in-days":3389,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Objective<\/jats:italic>. To compare the frequencies and responsiveness of rheumatoid factor (RF)\u2013producing B cells in the peripheral blood of patients with seronegative and seropositive rheumatoid arthritis (RA).<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic>. Frequencies of IgM+, IgG+, and RF+ B cells were determined by limiting\u2010dilution analysis of purified peripheral blood B cells from 6 patients with seropositive RA, 8 patients with seronegative RA, and 7 normal controls. B cell help was provided by cloned T helper cells, which were stimulated by either anti\u2010CD3 or the bacterial superantigen staphylococcal enterotoxin D (SED). IgM and IgG antibodies and RF in culture supernatants were detected by enzyme\u2010linked immunosorbent assay.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic>. In the presence of anti\u2010CD3\u2013stimulated T helper cells, 2\u201310% of B cells from normal individuals secreted IgM and IgG antibodies. The frequency of RF+ B cells was low and ranged from 1:182 to 1:885 (RF+: IgM+) B cells. In patients with seropositive RA, the numbers of Ig\u2010producing B cells were reduced by a factor of 2, while the fraction of RF+ B cell precursors was expanded by more than 50\u2010fold (7\u201320% of IgM+ B cells; <jats:italic>P<\/jats:italic> = 0.004). Patients with seronegative RA had higher frequencies of RF\u2010producing B cells (1.5\u20136% of IgM+ B cells) than normal individuals (<jats:italic>P<\/jats:italic> = 0.002), but not to the same extent as seropositive patients (<jats:italic>P<\/jats:italic> = 0.002). Stimulation of B cells using SED preferentially induced RF+ B cells in normal controls and in patients with seronegative and seropositive RA.<\/jats:p><jats:p><jats:italic>Conclusion<\/jats:italic>. B cell precursors with the potential to secrete RF were detectable in high frequencies in normal individuals and in patients with seropositive and seronegative RA. In all donors, these B cells could be stimulated with the bacterial superantigen SED. In normal individuals, RF+ B cells remained nonresponsive to help provided by anti\u2010CD3\u2013activated T cells, but were responsive in RA patients. Seronegative and seropositive RA form a continuous spectrum of disease, with a higher number of RF\u2010secreting B cells in the seropositive patients.<\/jats:p>","DOI":"10.1002\/art.1780390909","type":"journal-article","created":{"date-parts":[[2007,2,14]],"date-time":"2007-02-14T12:01:54Z","timestamp":1171454514000},"page":"1499-1506","source":"Crossref","is-referenced-by-count":5,"title":["Increased responsiveness of rheumatoid factor\u2013producing B cells in seronegative and seropositive rheumatoid arthritis"],"prefix":"10.1002","volume":"39","author":[{"given":"Xiaowen","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanyun","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy G.","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia M.","family":"Weyand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg J.","family":"Goronzy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,12]]},"reference":[{"key":"e_1_2_1_2_2","volume-title":"Textbook of Rheumatology","author":"Harris ED","year":"1993"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117900"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(08)60456-3"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.161.1.88"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI104523"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115007"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.05.040187.000545"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.173.2.487"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115239"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780360806"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401891"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780310302"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115634"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4049\/jimmunol.147.1.70","article-title":"Nonrandom selection of T cell specificities in anti\u2010HLA\u2010DR responses: sequence motifs of the responder HLA\u2010DR allele influence T cell recruitment","volume":"147","author":"Weyand CM","year":"1991","journal-title":"J Immunol"},{"key":"e_1_2_1_16_2","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.4049\/jimmunol.136.3.1038","article-title":"The immunosuppressive activity of L\u2010leucyl\u2010L\u2010leucine methylester: selective ablation of cytotoxic lymphocytes and monocytes","volume":"136","author":"Thiele DL","year":"1986","journal-title":"J Immunol"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.3.425"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.177.1.109"},{"key":"e_1_2_1_19_2","volume-title":"Human B\u2010Cell Superantigens","author":"Goronzy JJ"},{"key":"e_1_2_1_20_2","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.4049\/jimmunol.145.10.3155","article-title":"Frequency of human B cells that differentiate in response to anti\u2010CD3\u2010activated T cells","volume":"145","author":"Amoroso K","year":"1990","journal-title":"J Immunol"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.004313"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1993.1046"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.11.040193.001555"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.425"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117699"},{"key":"e_1_2_1_26_2","doi-asserted-by":"crossref","first-page":"5624","DOI":"10.4049\/jimmunol.152.12.5624","article-title":"Activation induces sensitivity toward APO\u20101 (CD95)\u2013mediated apoptosis in human B cells","volume":"152","author":"Daniel PT","year":"1994","journal-title":"J Immunol"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/368215a0"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.5.1847"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350809"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117040"},{"key":"e_1_2_1_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1992.tb00832.x"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116968"}],"container-title":["Arthritis &amp; 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