Abstract

We described a human regulatory T cell (Treg) population activated by IgG+ B cells presenting peptides of the heavy constant region (Fc) via processing of the surface IgG underlying a model for B cell-Treg cooperation in the human immune regulation. Functionally, Treg inhibited the polarization of naive T cells toward a pro-inflammatory phenotype in both a cognate and a non-cognate fashion. Their fine specificities were similar in healthy donors and patients with rheumatoid arthritis (RA), a systemic autoimmune disease. Four immunodominant Fc peptides bound multiple HLA class II alleles and were recognized by most subjects in the two cohorts. The presentation of Fc peptides that stimulate Treg through the processing of IgG by dendritic cells occurred in myeloid dendritic cells cDC1 and cDC2. Different routes of antigen processing of the IgG impacted Treg expansion in RA patients.

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