B cell homeostasis and the development of chronic graft-versus-host disease: implications for B cell-depleting therapy

Chronic graft-versus-host disease (GVHD) is a serious complication that develops frequently in survivors of allogeneic stem cell transplant. Since elucidation of the role of B cells in the pathogenesis of chronic GVHD, B cell-depleting therapy with rituximab has been associated with beneficial effects in clinical and laboratory studies in patients with chronic GVHD. Although the mechanism underlying the contribution of B cells to the development of chronic GVHD is poorly understood, recent studies have proposed that B cell reconstitution after allogeneic stem cell transplant is involved in the development of chronic GVHD. Inadequate reconstitution of naive B cells and the persistence of high levels of B cell-activating factor have been found in patients with chronic GVHD, and these changes might be associated with the expansion of activated CD27-positive B cells that produce autoantibody in chronic GVHD. In the light of this altered B cell homeostasis in chronic GVHD, the role of rituximab in controlling the clinical manifestations of chronic GVHD has been studied. In this review, we address the role of B cells in the pathogenesis of chronic GVHD and the response to B cell-depleting therapy based on B cell homeostasis.