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B cells regulate antidonor T-cell reactivity in transplantation. The analyses of indirect T-cell responses in patients with antibody-mediated renal transplant injury by Shiu et al. emphasize the complex contribution of B cells in alloimmunity. The data suggest at least three distinct but potentially overlapping consequences of T cell-B cell interactions: antigen presentation by B cells, alloantibody production, and immune regulation. These multifaceted functions of B cells should be taken into consideration in developing diagnostic tools and therapeutic strategies.