1. Transcriptionally Distinct B Cells Infiltrate Allografts After Kidney Transplantation.
- Author
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Zhang H, Cavazzoni CB, Hanson BL, Bechu ED, Podestà MA, Azzi J, Blazar BR, Chong AS, Kreisel D, Alessandrini A, and Sage PT
- Subjects
- Mice, Animals, Transplantation, Homologous, B-Lymphocytes, Antibodies, Allografts, Receptors, Antigen, B-Cell, Graft Rejection, Kidney Transplantation adverse effects
- 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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2023
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