B cells and T follicular helper lymphocytes
B cells are considered as major players in autoimmunity, not only by their antibody secretion but also considering their ability to cytokine secretion, antigen presentation to CD4+ T cells, and their contribution to tertiary lymphoid structure (TLS) formation.
T follicular helper (Tfh) cells are specialized providers of B cell help, and are essential for affinity maturation, and development of high affinity antibodies and memory B cells. As such, these cells have also been pointed out for their implication in the development of autoimmune diseases (AIDs) by both facilitating the aberrant generation of autoantibodies and promoting the formation of ectopic follicles.
Multiple sclerosis (MS) and rheumatoid arthritis (RA)
MS and RA are two inflammatory AIDs affecting the central nervous system and joints, respectively. Even if MS has long been considered as a T-cell mediated disease, immunoglobulin deposits and the efficacy of anti-CD20 antibodies strongly argue in favor of a crucial role for B cells in MS pathogenesis. Conversely, RA was thought to be a B-cell mediated AID due to the presence of specific autoantibodies. However, Th1 and Th17 cell involvement in RA pathogenesis is now well documented. These two AIDs also display organized TLS in specific inflammatory localizations, clustered B cells and specialized Tfh cells.
Expected results – Perspectives
We plan to focus on (1) deciphering Tfh cell contribution to autoimmune reaction either through their help to form TLS, or by directly supporting autoreactive B cell differentiation in plasma cells; (2) investigating IL-2 signaling in B cells as a contributor to AID pathogenesis. Addressing these two questions on representative groups of patients with AIDs should help to understand the role of Tfh/B cell crosstalk in both diseases, and to identify biological targets to normalize Tfh/B cell homeostasis.