Portal de Periódicos da CAPES

Long-Term Allograft Tolerance Is Characterized by the Accumulation of B Cells Exhibiting an Inhibited Profile

2010; Elsevier BV; Volume: 11; Issue: 3 Linguagem: Inglês

10.1111/j.1600-6143.2010.03336.x

1600-6143

Laëtitia Le Texier, Paméla Thébault, Amélie Lavault, Claire Usal, Emmanuel Mérieau, Thibaut Quillard, Béatrice Charreau, Jean Paul Soulillou, María Cristina Cuturi, Sophie Brouard, Elise Chiffoleau,

Renal Transplantation Outcomes and Treatments

Numerous reports have highlighted the central role of regulatory T cells in long-term allograft tolerance, but few studies have investigated the B-cell aspect. We analyzed the B-cell response in a rat model of long-term cardiac allograft tolerance induced by a short-term immunosuppression. We observed that tolerated allografts are infiltrated by numerous B cells organized in germinal centers that are strongly regulated in their IgG alloantibody response. Moreover, alloantibodies from tolerant recipients exhibit a deviation toward a Th2 isotype and do not activate in vitro donor-type endothelial cells in a pro-inflammatory way but maintained expression of cytoprotective molecules. Interestingly, this inhibition of the B-cell response is characterized by the progressive accumulation in the graft and in the blood of B cells blocked at the IgM to IgG switch recombination process and overexpressing BANK-1 and the inhibitory receptor Fcgr2b. Importantly, B cells from tolerant recipients are able to transfer allograft tolerance. Taken together, these results demonstrate a strong regulation of the alloantibody response in tolerant recipients and the accumulation of B cells exhibiting an inhibited and regulatory profile. These mechanisms of regulation of the B-cell response could be instrumental to develop new strategies to promote tolerance.