T cell–B cell interactions in human autoimmune diseases

Activation of autoreactive B cells and production of specific autoantibodies are hallmark features of many autoimmune diseases. B cell differentiation into antibody-secreting cells typically requires help from cognate T cells, which provide both cytokines and cell surface signals in an intricate intercellular interaction. A range of T cells can provide this help to B cells, including T follicular helper cells in follicles of secondary lymphoid organs, as well as T peripheral helper cells, which accumulate within inflamed target tissues in autoimmune diseases. Here, we discuss recent observations about the phenotypes of B cell–helper T cells that accumulate in inflamed tissues and in circulation of patients with autoimmune diseases, the correlations between B cell–helper T cells and B cells in these tissues, and key mediators of productive T cell–B cell interactions, with a focus on mediators that are being targeted therapeutically. Understanding the scope of B cell–helper T cells and their functions will improve our ability to quantify and track pathologic T cell–B cell interactions in human autoimmune diseases and may highlight critical mediators that can be targeted to suppress these interactions therapeutically.