Intrarenal B cells integrate in situ innate and adaptive immunity in human renal allograft rejection
Asano, Y.; Daccache, J.; Jain, D.; Ko, K.; Kinloch, A.; Veselits, M.; Wolfgeher, D.; Chang, A.; Josephson, M.; Cunningham, P.; Tambur, A.; Khan, A.; Pillai, S.; Chong, A. S.; Clark, M. R.
Show abstract
In human allograft rejection, intrarenal B cell infiltrates identify those with a poor prognosis. However, how intrarenal B cells contribute to rejection is not known. Single cell RNA-sequencing of intrarenal class-switched B cells revealed a unique innate cell transcriptional state resembling murine peritoneal B1 cells (Bin cells). Comparison to the transcriptome of whole renal allograft rejecting tissue revealed that Bin cells existed within a complex autocrine and paracrine network of signaling axes. The immunoglobulins expressed by Bin cells did not bind donor specific antigens nor were they enriched for reactivity to ubiquitously expressed self-antigens. Rather, Bin cells frequently expressed antibodies reactive with renal expressed antigens. Furthermore, local antigens could drive Bin cell proliferation and differentiation into plasma cells expressing self-reactive antibodies. By contributing to local innate immune networks, and expressing antibodies reactive with renal expressed antigens, Bin cells are predicted to amplify local inflammation and tissue destruction.
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