Transcriptionally Distinct B Cells Infiltrate Allografts after Kidney Transplantation

Hengcheng Zhang, Cecilia B. Cavazzoni, Benjamin L. Hanson, Elsa D. Bechu, Manuel A. Podestà, Jamil Azzi, Bruce R. Blazar, Anita S. Chong, Daniel Kreisel, Alessandro Alessandrini, Peter T. Sage

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background. Following allogeneic kidney transplantation, a substantial proportion of graft loss is attributed to the formation of donor-specific antibodies and antibody-mediated rejection. B cells infiltrate kidney grafts during antibody-mediated rejection; however, the origins, repertoires, and functions of these intrarenal B cells remain elusive. Methods. Here, we use murine allogeneic kidney transplant models to study the origins, transcriptional programming and B cell receptor repertoire of intragraft B cells, and in vitro stimulation assays to evaluate the ability of intragraft B cells to promote CD4+ T cell expansion. Results. B cells infiltrate kidney grafts in settings of allogeneic, but not syngeneic, transplantation. Intragraft B cells have characteristics of activation but are transcriptionally distinct from germinal center B cells and resemble innate-like B cells. B cell receptor sequencing demonstrates that the majority of intragraft B cells do not originate from lymph node germinal center B cells and are largely germline. Class-switched intragraft B cells are rare but can be donor-specific and produce IgG capable of binding to the kidney allograft. Lastly, intrarenal B cells are capable of stimulating naive T cells but have an altered ability to promote T follicular helper cell expansion. Conclusions. Together, these data demonstrate that intrarenal B cells during transplant rejection are transcriptionally distinct from lymph node B cells.

Original languageEnglish (US)
Pages (from-to)E47-E57
JournalTransplantation
Volume107
Issue number2
DOIs
StatePublished - Feb 1 2023

Bibliographical note

Funding Information:
This work was supported by the National Institute of Health through grants P01AI056299 and R01AI153124.

Publisher Copyright:
© Copyright 2022 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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