Late B lymphocyte action in dysfunctional tissue repair following kidney injury and transplantation

Abstract

The mechanisms initiating the late immune response to allografts are poorly understood. Through transcriptome analysis of serial protocol biopsies in kidney transplant recipients, we found a tight correlation between the initial response to kidney injury and a late B lymphocyte signature associated with renal dysfunction and fibrosis, suggesting a link between dysfunctional repair and immunoreactivity. To specifically investigate the immunological consequences of dysfunctional repair, we followed the mouse kidney up to 18 months after ischemia/reperfusion. Even in the absence of foreign antigens we identified a sustained immune response in conjunction with the transition to chronic kidney damage. This tissue-driven immunological process involved both the innate and the adaptive immune system and eventually induced an antigen-driven proliferation, selection and maturation of B lymphocytes into broadly-reacting antibody secreting cells. These findings reveal an unappreciated role of dysfunctional tissue repair on local immunoregulation with a particular relevance for late transplantation immunobiology.