Chronic graft-versus-host disease (cGVHD) is a common complication in patients after receiving an allogeneic tissue transplant, such as hematopoietic stem cell transplantation from unrelated donors.  cGVHD was viewed predominantly as a T-cell mediated disease but the emerging evidences indicate the crucial role of B-cell and other immune cells in its pathogenesis.  In their original paper in Blood [1], Flynn et al. show that increased frequency of T follicular helper (Tfh) cells and germinal center (GC) B-cells correlates with the development of cGVHD in a murine model and that blocking monoclonal antibodies (mAbs) for interleukin-21 (IL-21), inducble T-cell costimulator(ICOS) and CD40 ligand reverse cGVHD. These data demonstrate the importance of T follicular helper (Tfh) and germinal center (GC) B-cells in the pathogenesis of cGVHD and associated bronchiolitis obliterans syndrome (BOS) and suggest that new therapies using monoclonal antibodies (mAbs) targetingTfh cells, GC B cells, and their interactions could potentially reverse established pulmonary cGVHD.