B cells in rheumatoid arthritis synovial tissues encode focused antibody repertoires that include antibodies that stimulate macrophage TNF-a production. Clinical immunology (Orlando, Fla.) Elliott, S. E., Kongpachith, S. n., Lingampalli, N. n., Adamska, J. Z., Cannon, B. J., Blum, L. K., Bloom, M. S., Henkel, M. n., McGeachy, M. J., Moreland, L. W., Robinson, W. H. 2020: 108360

Abstract

Rheumatoid arthritis (RA) is characterized by the production of anti-citrullinated protein antibodies (ACPAs). To gain insights into the relationship between ACPA-expressing B cells in peripheral blood (PB) and synovial tissue (ST), we sequenced the B cell repertoire in paired PB and ST samples from five individuals with established, ACPA+ RA. Bioinformatics analysis of paired heavy and light chain sequences revealed clonally-related family members shared between PB and ST. ST-derived antibody repertoires exhibited reduced diversity and increased normalized clonal family size compared to PB-derived repertoires. Functional characterization showed that seven recombinant antibodies (rAbs) expressed from subject-derived sequences from both compartments bound citrullinated antigens and immune complexes (ICs) formed using one ST-derived rAb stimulated macrophage TNF-a production. Our findings demonstrate B cell trafficking between PB and ST in subjects with RA and ST repertoires include B cells that encode ACPA capable of forming ICs that stimulate cellular responses implicated in RA pathogenesis.

View details for DOI 10.1016/j.clim.2020.108360

View details for PubMedID 32035179