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

Nat Commun. 2021 Jul 16;12(1):4372. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts / immunology*
  • Animals
  • Autoantibodies / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Gene Ontology
  • Graft Rejection / immunology*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Inflammation / metabolism*
  • Kidney / immunology
  • Kidney / metabolism
  • Kidney Transplantation / adverse effects*
  • Mice
  • Palatine Tonsil / immunology
  • Palatine Tonsil / metabolism
  • RNA-Seq
  • Single-Cell Analysis
  • Transplantation, Homologous


  • Autoantibodies
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunoglobulin G