B cells play a crucial role in alloreactivity of organ transplant rejection and graft versus host diseases (GVHD). Over the past decade, it has been well recognized that B-cell infiltration in allografts and de novo donor-specific antibodies (DSA) were strongly associated with severe graft rejection and loss, as well as glucocorticoid resistance. Emerging evidence has demonstrated that Follicular T helper (Tfh) cells are key effectors to promote the proliferation and differentiation of B cells into antibody-producing plasmablasts and memory B cells. T-follicular regulatory (Tfr) cells are a recently recognized cell population that has a negative regulatory role on Tfh cells in the follicle, preventing incessant antibody production. It is still less clear how those humoral immunoreactive cells affect transplant rejection and allograft loss. This review focuses on the production and function of Tfr/Tfh cells in the transplant environment. Better understanding of the functions and mechanisms of Tfr/Tfh cells will help to design new strategies to prevent allograft rejection and prolong graft survival.
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