AbstractThe bone marrow (BM) is responsible for generating and maintaining lifelong output of blood and immune cells. In addition to its key hematopoietic function, the BM acts as an important lymphoid organ, hosting a large variety of mature lymphocyte populations, including B cells, T cells, natural killer T cells, and innate lymphoid cells. Many of these cell types are thought to visit the BM only transiently, but for others, like plasma cells and memory T cells, the BM provides supportive niches that promote their long-term survival. Interestingly, accumulating evidence points toward an important role for mature lymphocytes in the regulation of hematopoietic stem cells (HSCs) and hematopoiesis in health and disease. In this review, we describe the diversity, migration, localization, and function of mature lymphocyte populations in murine and human BM, focusing on their role in immunity and hematopoiesis. We also address how various BM lymphocyte subsets contribute to the development of aplastic anemia and immune thrombocytopenia, illustrating the complexity of these BM disorders and the underlying similarities and differences in their disease pathophysiology. Finally, we summarize the interactions between mature lymphocytes and BM resident cells in HSC transplantation and graft-versus-host disease. A better understanding of the mechanisms by which mature lymphocyte populations regulate BM function will likely improve future therapies for patients with benign and malignant hematologic disorders.