Working model of how donor-derived antibodies may help perpetuate cGVHD immune pathology. GCs are required for production of disease-inciting alloantibody early in the disease process. Due to altered T- and B-cell homeostasis, aberrant B cells develop over time that produce antibodies directed against primary (1°) and secondary (2°) lymphoid organs. Lymphoid-organ damage perpetuates loss of immune tolerance and the promotion of cGVHD of the skin. T_reg, regulatory T cell.