Innate-like self-reactive B cells infiltrate human renal allografts during transplant rejection

• Published in: Nature communications Vol. 12; no. 1; p. 4372
• Main Authors: Asano, Yuta, Daccache, Joe, Jain, Dharmendra, Ko, Kichul, Kinloch, Andrew, Veselits, Margaret, Wolfgeher, Donald, Chang, Anthony, Josephson, Michelle, Cunningham, Patrick, Tambur, Anat, Khan, Aly A., Pillai, Shiv, Chong, Anita S., Clark, Marcus R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 38; 38/91; 45; 631/250/1619/40/1906; 631/250/1854; 631/250/2152/569/2495; 82/1; 82/51; 82/58; Allografts; Antibodies; Antigens; Autoantigens; Cell differentiation; Cell proliferation; Gene sequencing; Graft rejection; Humanities and Social Sciences; Immunological tolerance; Inflammation; Kidney transplantation; Lymphocytes B; multidisciplinary; Peritoneum; Plasma cells; Prognosis; Rejection; Science; Science (multidisciplinary); Transcription
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24615-6

Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. Here we show using single-cell RNA sequencing that intrarenal class-switched B cells have an innate cell transcriptional state resembling mouse peritoneal B1 or B-innate (Bin) cells. Antibodies generated by Bin cells do not bind donor-specific antigens nor are they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently express antibodies reactive with either renal-specific or inflammation-associated antigens. Furthermore, local antigens can drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. These data show a mechanism of human inflammation in which a breach in organ-restricted tolerance by infiltrating innate-like B cells drives local tissue destruction. Intrarenal B cells are indicative of poor prognosis in human renal allografts. Here the authors use single cell RNA sequencing to examine how intrarenal B cells contribute to renal rejection and find a population of innate B cells reactive to renal-specific or inflammation-associated antigens.