B cells polarize pathogenic inflammatory T helper subsets through ICOSL-dependent glycolysis.

B cells constitute abundant cellular components in inflamed human tissues, but their role in pathogenesis of inflammatory T helper (T) subsets is still unclear. Here, we demonstrate that B cells, particularly resting naïve B cells, have a previously unrecognized helper function that is involved in shaping the metabolic process and subsequent inflammatory differentiation of T-cell receptor-primed T cells. ICOS/ICOSL axis-mediated glucose incorporation and utilization were crucial for inflammatory T subset induction by B cells, and activation of mTOR was critical for T cell glycolysis in this process. Consistently, upon encountering ICOSL B cells, activated effector memory T cells from patients with rheumatoid arthritis or systemic lupus erythematosus spontaneously differentiated into inflammatory T subsets. Immunotherapy using rituximab that specifically depleted B cells in patients with rheumatoid arthritis efficiently abrogated the capabilities of memory T cells to incorporate and use glucose, thereby impairing the pathogenic differentiation of inflammatory T subsets.