Pathophysiologic significance of B-cell clusters in chronically rejected grafts

The role of antibodies in the pathogenesis of chronic rejection is increasingly acknowledged. In contrast, whether B-cell clusters, which have been recently identified in chronically rejected allografts, actively participate in the process or are only an epiphenomenon remain a matter of debate. Integrating recently published data, we put forward explanations that reconcile the conflicting conclusions of experimental and biopsy-based studies. Finally, we propose a unified model in which B-cell clusters as part of intragraft tertiary lymphoid tissue can play deleterious or regulatory roles and therefore actively modulate the kinetics of chronic rejection.