AUTHOR=Julé Amélie M. , Lam Ki Pui , Taylor Maria , Hoyt Kacie J. , Wei Kevin , Gutierrez-Arcelus Maria , Case Siobhan M. , Chandler Mia , Chang Margaret H. , Cohen Ezra M. , Dedeoglu Fatma , Halyabar Olha , Hausmann Jonathan , Hazen Melissa M. , Janssen Erin , Lo Jeffrey , Lo Mindy S. , Meidan Esra , Roberts Jordan E. , Wobma Holly , Son Mary Beth F. , Sundel Robert P. , Lee Pui Y. , Sage Peter T. , Chatila Talal A. , Nigrovic Peter A. , Rao Deepak A. , Henderson Lauren A. 

TITLE=Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1068399

DOI=10.3389/fimmu.2022.1068399

ISSN=1664-3224

ABSTRACT=<p>T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.</p>