Harnessing regulatory B cells to prevent experimental obliterative bronchiolitis

Lung transplantation (LTx) is a lifesaving procedure for several end-stage lung diseases. Despite medical and surgical improvements, the outcome after LTx remains worse when compared with the transplant of other solid transplantable organs. The major obstacle to long-term survival after LTx is chronic rejection, histologically described as obliterative bronchiolitis (OB). To find new therapeutic approaches for the amelioration of OB, novel targets in basic science need to be challenged. In this issue of the Journal, Lau and colleagues describe the demonstration that in an established experimental model of OB, the heterotopic tracheal transplantation model, the mammalian (mechanistic) target of rapamycin inhibitor reduces OB development and increases the infiltration of B cells into allografts. By means of immunohistochemical and immunofluorescence studies, Lau and colleagues determined these B cells to be of a regular phenotype, expressing interleukin (IL)10 and transforming growth factor b1. These regulatory B cells (Bregs) further stimulated the production and activation of regulatory T cells,and togethertheylimited theinflammatory process after LTx by downregulating proinflammatory cytokines and overexpressing anti-inflammatory cytokines. B cells are traditionally recognized as important contributors of chronic graft failure by virtue of antigen presentation, T-cell coactivation, and the production of donor-specific antibodies. 1 This has been particularly shown in experimental 2 but also human clinical OB. 3