Imbalance favoring follicular helper T cells over IL10⁺ regulatory B cells is detrimental for the kidney allograft

A high frequency of regulatory B (Breg) cells, generally transitional B cells, has been associated with long-term kidney allograft survival and operational tolerance. However, circulating follicular helper T cells (cTfh) correlate with graft rejection. In order to better understand the interplay between these cell subsets and to determine their association with graft outcome we studied transitional and IL10⁺ Breg cells, as well as cTfh, pre- and post-transplantation in a prospective cohort of 200 kidney transplant recipients and in healthy volunteers. Patients with end-stage kidney disease had higher frequencies of transitional and IL10⁺ Breg cells compared to controls, and these subsets decreased during the one-year post-transplant follow-up. Higher frequencies of pre-transplant IL10⁺ Breg cells, and a larger reduction in these cells early post-transplantation, predicted acute rejection and graft failure. Moreover, IL10⁺ Breg cells correlated with cTfh pre-transplantation, and a post-transplant increase in the cTfh/IL10⁺Breg ratio preceded acute rejection. Thus, evaluation of pre-transplant IL10⁺ Breg cells and the regular monitoring of the cTfh/IL10⁺Breg ratio may be useful to assess post-transplant risk. Hence, our observations suggest the need to develop therapeutic strategies aimed at preserving regulatory B cells, and depleting Tfh, post-transplantation.