{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T14:01:47Z","timestamp":1793109707106,"version":"4.5.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T00:00:00Z","timestamp":1639526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Antinuclear antibody (ANA)\u2013positive juvenile idiopathic arthritis (JIA) is characterized by synovial B cell hyperactivity, but the precise role of CD4+ T cells in promoting local B cell activation is unknown. This study was undertaken to determine the phenotype and function of synovial CD4+ T cells that promote aberrant B cell activation in JIA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Flow cytometry was performed to compare the phenotype and cytokine patterns of PD\u20101<jats:sup>high<\/jats:sup>CD4+ T cells in the synovial fluid (SF) of patients with JIA and T follicular helper cells in the tonsils of control individuals. <jats:italic>TCRVB<\/jats:italic> next\u2010generation sequencing was used to analyze T cell subsets for signs of clonal expansion. The functional impact of these T cell subsets on B cells was examined in cocultures in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multidimensional flow cytometry revealed the expansion of interleukin\u201021 (IL\u201021) and interferon\u2010\u03b3 (IFN\u03b3)\u2013coexpressing PD\u20101<jats:sup>high<\/jats:sup>CXCR5\u2013HLA\u2013DR+CD4+ T cells that accumulate in the joints of ANA\u2010positive JIA patients. These T cells exhibited signs of clonal expansion with restricted T cell receptor clonotypes. The phenotype resembled peripheral T helper (Tph) cells with an extrafollicular chemokine receptor pattern and high T\u2010bet and B lymphocyte\u2013induced maturation protein 1 expression, but low B cell lymphoma 6 expression. SF Tph cells, by provision of IL\u201021 and IFNy, skewed B cell differentiation toward a CD21<jats:sup>low\/\u2013<\/jats:sup>CD11c+ phenotype in vitro. Additionally, SF Tph cell frequencies correlated with the appearance of SF CD21<jats:sup>low\/\u2013<\/jats:sup>CD11c+CD27\u2013IgM\u2013 double\u2010negative (DN) B cells in situ.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Clonally expanded CD4+ Tph cells accumulate in the joints of ANA\u2010positive JIA patients and, in particular, promote CD21<jats:sup>low\/\u2013<\/jats:sup>CD11c+\u2009DN B cell differentiation. The expansion of Tph cells and DN B cells might reflect the autoimmune response in the joints of ANA\u2010positive JIA patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41913","type":"journal-article","created":{"date-parts":[[2021,7,2]],"date-time":"2021-07-02T00:10:57Z","timestamp":1625184657000},"page":"150-162","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Effect of Clonally Expanded <scp>PD\u20101<sup>high<\/sup>CXCR5<\/scp>\u2013<scp>CD4<\/scp>+ Peripheral T Helper Cells on B Cell Differentiation in the Joints of Patients With Antinuclear Antibody\u2013Positive Juvenile Idiopathic Arthritis"],"prefix":"10.1002","volume":"74","author":[{"given":"Jonas","family":"Fischer","sequence":"first","affiliation":[{"name":"University of W\u00fcrzburg  W\u00fcrzburg 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