Feeding the fire: the role of defective bone marrow function in exacerbating thymic involution

Most of the steps of lymphopoiesis have been elucidated but contentious issues remain, particularly regarding the identity and function of the earliest lymphoid progenitors that leave the bone marrow and seed the thymus. Hematopoiesis is effectively continuous throughout life, but there is a profound decline in immune function with increasing age, driven by thymus involution and severely curtailed B cell development. A key question is whether defects in bone marrow progenitors, such as reduced differentiation and repopulation potential, are the common denominator. While thymic involution temporally precedes overt HSC functional decline, a logical supposition is that the latter exacerbates the former. This review explores this possible link, and concludes that improving bone marrow function is fundamental to sustained thymic regeneration.