Abstract
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.
Highlights
Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear
One clear pathogenic function of B cells is the secretion of donor-specific antibodies (DSAs) that recognize donor human leukocyte antigen (HLA)
In ongoing renal allograft rejection, the antigens driving in situ B cell selection, and the magnitude of that selection, remain unknown
Summary
Intrarenal B cells in human renal allografts indicate transplant recipients with a poor prognosis, but how these cells contribute to rejection is unclear. 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. It is not known if infiltrating B cells express DSAs in ongoing rejection In both mice and humans, renal transplant rejection can be associated with loss of tolerance and serum antibodies to selfantigens[22]. It is not known how and where tolerance to self is broken in allograft recipients who do not have an underlying autoimmune disease. In ongoing renal allograft rejection, the antigens driving in situ B cell selection, and the magnitude of that selection, remain unknown
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