{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T22:42:41Z","timestamp":1781304161763,"version":"3.54.1"},"reference-count":47,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T00:00:00Z","timestamp":1538092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["NSC99\u20102320\u2010B\u2010002\u2010011"],"award-info":[{"award-number":["NSC99\u20102320\u2010B\u2010002\u2010011"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis & Rheumatology"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Objective<\/jats:title>Fc\u03b3 receptor II<\/jats:styled-content>b (Fc\u03b3RII<\/jats:styled-content>b) is an essential negative regulator of B cells that blocks B cell receptor (BCR<\/jats:styled-content>) signaling and triggers c\u2010Abl\u2013dependent apoptosis of B cells. Fc\u03b3RII<\/jats:styled-content>b\u2010deficient mice display splenomegaly with expansion of B cells, leading to lupus. Fc\u03b3RII<\/jats:styled-content>b\u2010I232T is a hypofunctional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of the Fc\u03b3RII<\/jats:styled-content>b\u2010I232T polymorphism, we investigated the role of Fc\u03b3RII<\/jats:styled-content>b in the deletion of low\u2010affinity germinal center (GC<\/jats:styled-content>) B cells, an important mechanism for preventing autoimmunity.<\/jats:p><\/jats:sec>Methods<\/jats:title>We generated Fc\u03b3RII<\/jats:styled-content>b232T\/T<\/jats:sup> mice to mimic human Fc\u03b3RII<\/jats:styled-content>b\u2010I232T carriers and immunized mice with chicken gamma globulin (CGG<\/jats:styled-content>)\u2013conjugated NP<\/jats:styled-content>, a T cell\u2013dependent antigen, to examine the response of GC<\/jats:styled-content> B cells.<\/jats:p><\/jats:sec>Results<\/jats:title>Compared to wild\u2010type (WT<\/jats:styled-content>) mice, Fc\u03b3RII<\/jats:styled-content>b232T\/T<\/jats:sup> mice showed increased numbers of low\u2010affinity NP<\/jats:styled-content>\u2010specific IgG and NP<\/jats:styled-content>\u2010specific B cells and plasma cells; additionally, the expression of a somatic mutation (W33L) in their VH<\/jats:sub><\/jats:styled-content>186.2 genes encoding high\u2010affinity BCR<\/jats:styled-content> was reduced. Notably, Fc\u03b3RII<\/jats:styled-content>b232T\/T<\/jats:sup> mice had a higher number of GC<\/jats:styled-content> light zone B cells and showed less apoptosis than WT<\/jats:styled-content> mice, despite having equivalent follicular helper T cell numbers and function. Moreover, phosphorylation of c\u2010Abl was reduced in Fc\u03b3RII<\/jats:styled-content>b232T\/T<\/jats:sup> mice, and treatment of WT<\/jats:styled-content> mice with the c\u2010Abl inhibitor nilotinib during the peak of GC<\/jats:styled-content> response resulted in reduced affinity maturation reminiscent of Fc\u03b3RII<\/jats:styled-content>b232T\/T<\/jats:sup> mice.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings provide evidence of a critical role of Fc\u03b3RII<\/jats:styled-content>b\/c\u2010Abl in the negative selection of GC<\/jats:styled-content> B cells in Fc\u03b3RII<\/jats:styled-content>b232T\/T<\/jats:sup> mice. Importantly, our findings indicate potential benefits of up\u2010regulating Fc\u03b3RII<\/jats:styled-content>b expression in B cells for treatment of systemic lupus erythematosus.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.40555","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T02:40:26Z","timestamp":1526611226000},"page":"1866-1878","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Lupus\u2010Associated Fc\u03b3 Receptor IIb\u2013I232T Polymorphism Results in Impairment in the Negative Selection of Low\u2010Affinity Germinal Center B Cells Via c\u2010Abl in Mice"],"prefix":"10.1002","volume":"70","author":[{"given":"Jyun\u2010Pei","family":"Jhou","sequence":"first","affiliation":[{"name":"National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u2010Shing","family":"Yu","sequence":"additional","affiliation":[{"name":"National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haw","family":"Hwai","sequence":"additional","affiliation":[{"name":"National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Shan","family":"Chen","sequence":"additional","affiliation":[{"name":"National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Lung","family":"Chen","sequence":"additional","affiliation":[{"name":"National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiang\u2010Jong","family":"Tzeng","sequence":"additional","affiliation":[{"name":"National Taiwan University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,28]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"131","article-title":"Fc receptors as adaptive immunoreceptors","volume":"382","author":"Daeron M","year":"2014","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12368"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00027-3"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100171"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505308200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.4049\/jimmunol.157.6.2234","article-title":"Negative signaling in B lymphocytes induces tyrosine phosphorylation of the 145\u2013kDa inositol polyphosphate 5\u2013phosphatase, SHIP","volume":"157","author":"Chacko GW","year":"1996","journal-title":"J Immunol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-2478(96)02653-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/383263a0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80074-6"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2003.00047.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.22220"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915133107"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi320"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.2.793"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160528"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608889104"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017996108"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051503"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.5.3272"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxm132"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.3.1440"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1986.tb01484.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2658060"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13300"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.001001"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3804"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902530"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.12.6268"},{"key":"e_1_2_7_30_1","first-page":"e54582","article-title":"The isolation, differentiation, and quantification of human antibody\u2013secreting B cells from blood: ELISpot as a functional readout of humoral immunity","volume":"118","author":"Tzeng SJ","year":"2016","journal-title":"J Vis Exp"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-015-0200-9"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2428"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp352"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.46.73"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011550"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.3.679"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.5.781"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201242809"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241680"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1257861"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.3.399"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80471-9"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.3.475"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni924"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00323-6"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.5.2019"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072565"}],"container-title":["Arthritis & Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fart.40555","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.40555","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T11:30:12Z","timestamp":1759923012000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.40555"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,28]]},"references-count":47,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/art.40555"],"URL":"https:\/\/doi.org\/10.1002\/art.40555","archive":["Portico"],"relation":{},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,28]]},"assertion":[{"value":"2017-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}