PT  - JOURNAL ARTICLE
AU  - Pietro E Cippà
AU  - Jing Liu
AU  - Bo Sun
AU  - Sanjeev Kumar
AU  - Maarten Naesens
AU  - Andrew P McMahon
TI  - Late B lymphocyte action in dysfunctional tissue repair following kidney injury and transplantation
AID  - 10.1101/343012
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 343012
4099  - http://biorxiv.org/content/early/2018/06/08/343012.short
4100  - http://biorxiv.org/content/early/2018/06/08/343012.full
AB  - 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.