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

• Published in: Nature communications 2019-03, Vol.10 (1), p.1157-11, Article 1157
• Main Authors: Cippà, Pietro E., Liu, Jing, Sun, Bo, Kumar, Sanjeev, Naesens, Maarten, McMahon, Andrew P.
• Format: Article
• Language: English
• Subjects: 13/1; 13/51; 14/63; 38/23; 38/91; 49/31; 631/250/1854/2812; 631/250/2152/2153; 631/250/256/2515; 64/60; 692/4022/1585/104; Acute Kidney Injury - immunology; Acute Kidney Injury - pathology; Acute Kidney Injury - physiopathology; Adaptive Immunity; Adaptive systems; Adult; Allografts - cytology; Allografts - immunology; Allografts - pathology; Allografts - physiopathology; Animals; Antigens; B-Lymphocytes - immunology; Biopsy; Cell proliferation; Chronic illnesses; Disease Models, Animal; Female; Fibrosis; Gene expression; Gene Expression Profiling; Glomerular Filtration Rate; Graft Rejection - immunology; Graft Rejection - pathology; Graft Rejection - physiopathology; Humanities and Social Sciences; Humans; Immune response; Immune system; Immunology; Immunomodulation; Immunoreactivity; Injuries; Ischemia; Kidney - cytology; Kidney - immunology; Kidney - pathology; Kidney - physiopathology; Kidney transplantation; Kidney Transplantation - adverse effects; Kidneys; Lymphocytes; Lymphocytes B; Male; Mice; Mice, Inbred C57BL; Middle Aged; multidisciplinary; Renal function; Renal Insufficiency, Chronic - immunology; Renal Insufficiency, Chronic - pathology; Renal Insufficiency, Chronic - physiopathology; Repair; Reperfusion; Reperfusion Injury - immunology; Reperfusion Injury - pathology; Reperfusion Injury - physiopathology; Science; Science (multidisciplinary); Sequence Analysis, RNA; Transplantation; Transplantation, Homologous - adverse effects; Transplants; Transplants & implants
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-09092-2

The mechanisms initiating late immune responses to an allograft are poorly understood. Here we show, via transcriptome analysis of serial protocol biopsies from kidney transplants, that the initial responses to kidney injury correlate with a late B lymphocyte signature relating to renal dysfunction and fibrosis. With a potential link between dysfunctional repair and immunoreactivity, we investigate the immunological consequences of dysfunctional repair examining chronic disease in mouse kidneys 18 months after a bilateral ischemia/reperfusion injury event. In the absence of foreign antigens, a sustained immune response involving both innate and adaptive immune systems accompanies a transition to chronic kidney damage. At late stages, B lymphocytes exhibite an antigen-driven proliferation, selection and maturation into broadly-reacting antibody-secreting cells. These findings reveal a previously unappreciated role for dysfunctional tissue repair in local immunomodulation that may have particular relevance to transplant-associated immunobiology. Allograft can induces local chronic inflammation, but how this feeds back to regulating late immunity is still not clear. Here the authors show, by charactering B cell transcriptome landscape dynamic in human allografts and in mouse kidneys transitioning from acute to chronic injury, that late B cell activation is associated with renal dysfunction and inflammation.