Graft-versus-host disease (GVHD) has posed many challenges in allogeneic HSCT. Thanks to the development of immunomodulating approaches, the mortality of acute GVHD (aGVHD) is drastically decreased. Nevertheless, chronic GVHD (cGVHD) is became the leading causes of death in patients who survived of aGVHD. Various studies have demonstrated the essential role of B cells in the development of cGVHD. B cells are directly involved in allogeneic reactions through a variety of mechanisms such as alloantibody production, triggering complement system, promoting antibody-dependent cellular cytotoxicity (ADCC), and cross-presentation of immune complexes. It has been known that the pathways involved in the B-cell homeostasis and survival, such as BAFF, BCR, and Notch2 signaling pathways are abnormal in cGVHD. Post-HSCT lymphopenia triggers the continuous release of BAFF, leading to abnormalities in B cell homeostasis, and increasing the survival of alloreactive/autoreactive B cells, leading to production of allo/auto-antibodies. On the other hand, reduction of regulatory B cells following HSCT, causes loss of T cell peripheral tolerance, leading to cGVHD incidence. Therefore, B cells deserve special consideration in allogeneic HSCT, and targeting alloreactive B cells might be a promising approach in cGVHD management. In this article, we discussed the role of B cells in pathophysiology of cGVHD.

Keywords: Chronic graft-versus-host disease, Hematopoietic stem cell transplantation, B cell, BAFF