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B cell\u2013activating factor (BAFF) and a proliferation\u2010inducing ligand (APRIL) are the members of membrane proteins Type 2 family released by proteolytic cleavage of furin to form active, soluble homotrimers. Except for B cells, ligands are expressed by all such immune cells like T cells, dendritic cells, monocytes, and macrophages. BAFF and APRIL have two common receptors, namely TNFR homolog transmembrane activator and Ca2+ modulator and CAML interactor (TACI) and B cell\u2013maturation antigen. BAFF alone can also be coupled with a third receptor called BAFFR (also called BR3 or BLyS Receptor). These receptors are often expressed by immune cells in the B\u2010cell lineage. The binding of BAFF or APRIL to their receptors supports B cells differentiation and proliferation, immunoglobulin production and the upregulation of B cell\u2013effector molecules expression. It is possible that the overexpression of BAFF and APRIL contributes to the pathogenesis of autoimmune diseases. In BAFF transgenic mice, there is a pseudo\u2010autoimmune manifestation, which is associated with an increase in B\u2010lymphocytes, hyperglobulinemia, anti\u2010single stranded DNA, and anti\u2010double\u2010stranded DNA antibodies, and immune complexes in their peripheral blood. Furthermore, overexpressing BAFF augments the number of peripheral B220+ B cells with a normal proliferation rate, high levels of Bcl2, and prolonged survival and hyperactivity. Therefore, in this review article, we studied BAFF and APRIL as important mediators in B\u2010cell and discussed their role in rheumatoid arthritis.<\/jats:p>","DOI":"10.1002\/jcp.28445","type":"journal-article","created":{"date-parts":[[2019,4,3]],"date-time":"2019-04-03T00:54:46Z","timestamp":1554252886000},"page":"17050-17063","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":86,"title":["The role of BAFF and APRIL in rheumatoid arthritis"],"prefix":"10.1002","volume":"234","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4651-5635","authenticated-orcid":false,"given":"Arezoo G.","family":"Shabgah","sequence":"first","affiliation":[{"name":"Immunology Research Center Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaleh","family":"Shariati\u2010Sarabi","sequence":"additional","affiliation":[{"name":"Rheumatic Diseases Research Center Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jalil","family":"Tavakkol\u2010Afshari","sequence":"additional","affiliation":[{"name":"Immunology Research Center Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0088-5916","authenticated-orcid":false,"given":"Mojgan","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Immunology Research Center Mashhad University of Medical Sciences Mashhad Iran"},{"name":"Allergy Research Center Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,2]]},"reference":[{"key":"e_1_2_13_1_2_1","volume-title":"BAFF system in rheumatoid arthritis: from pathobiology to therapeutic targets","author":"Ancuta C.","year":"2017"},{"issue":"3","key":"e_1_2_13_1_3_1","first-page":"368","article-title":"One year in review 2017: Pathogenesis of rheumatoid arthritis","volume":"35","author":"Angelotti F.","year":"2017","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_13_1_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-110858"},{"issue":"7","key":"e_1_2_13_1_5_1","first-page":"1256","article-title":"Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis","volume":"35","author":"Bosello S.","year":"2008","journal-title":"The Journal of Rheumatology"},{"key":"e_1_2_13_1_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-110874"},{"key":"e_1_2_13_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201040591"},{"key":"e_1_2_13_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.09.004"},{"key":"e_1_2_13_1_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5335.138"},{"key":"e_1_2_13_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00130-3"},{"key":"e_1_2_13_1_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0688-0"},{"key":"e_1_2_13_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2014.11.002"},{"key":"e_1_2_13_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2015.01.001"},{"key":"e_1_2_13_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO;2-S"},{"key":"e_1_2_13_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.01.021"},{"key":"e_1_2_13_1_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-015-3372-4"},{"key":"e_1_2_13_1_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1505-8"},{"key":"e_1_2_13_1_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.9.5947"},{"key":"e_1_2_13_1_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kev252"},{"key":"e_1_2_13_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38950"},{"key":"e_1_2_13_1_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-10-3123"},{"key":"e_1_2_13_1_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.23047"},{"key":"e_1_2_13_1_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi048227k"},{"key":"e_1_2_13_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00728-4"},{"key":"e_1_2_13_1_25_1","first-page":"491","article-title":"BLyS levels in sera of patients with systemic lupus erythematosus: Clinical and serological correlation","author":"Elbirt D.","year":"2014","journal-title":"The Israel Medical Association Journal"},{"issue":"3","key":"e_1_2_13_1_26_1","first-page":"67","article-title":"Relationship of serum BAFF levels and BAFF receptor (BAFF\u2010R) expression on B lymphocytes in early and late rheumatoid arthritis Egyptian patients","volume":"7","author":"Elsaeed A. 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