Memory B Cells Activate Brain-Homing, Autoreactive CD4⁺ T Cells in Multiple Sclerosis.

ABSTRACT: Multiple sclerosis is an autoimmune disease that is caused by the interplay of genetic, particularly the HLA-DR15 haplotype, and environmental risk factors. How these etiologic factors contribute to generating an autoreactive CD4⁺ T cell repertoire is not clear. Here, we demonstrate that self-reactivity, defined as "autoproliferation" of peripheral Th1 cells, is elevated in patients carrying the HLA-DR15 haplotype. Autoproliferation is mediated by memory B cells in a HLA-DR-dependent manner. Depletion of B cells in vitro and therapeutically in vivo by anti-CD20 effectively reduces T cell autoproliferation. T cell receptor deep sequencing showed that in vitro autoproliferating T cells are enriched for brain-homing T cells. Using an unbiased epitope discovery approach, we identifi

SUBMITTER: Jelcic I 

PROVIDER: S-EPMC6191934 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature