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bioRxiv · 10.1101/343012

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

Cippa, P.·Liu, J.·Sun, B.·Kumar, S.·Naesens, M.·McMahon, A. P.
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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.

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Cippa, P., Liu, J., Sun, B., Kumar, S., Naesens, M., McMahon, A. P.. 2018-06-08. Late B lymphocyte action in dysfunctional tissue repair following kidney injury and transplantation. https://doi.org/10.1101/343012

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