Human Kidneys House Tissue-Resident B Cells with a Distinct Anatomical Location and Phenotype that Changes with Age
- Transplantation: Basic
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
- 2101 Transplantation: Basic
- Suchanek, Ondrej, University of Cambridge, Cambridge, United Kingdom
- Stewart, Benjamin James, University of Cambridge, Cambridge, United Kingdom
- Clatworthy, Menna R., University of Cambridge, Cambridge, United Kingdom
B cells play a central role in humoral immunity but have also antibody-independent functions, important for generating local immune responses and tolerance. Kidneys are the most commonly transplanted solid organ worldwide but whether they harbor B cells in homeostasis and how they change with donor age has received little attention.
We examined the number, phenotype and clonality of B cells in human kidneys that were perfused to remove circulating cells, and in matched splenic tissue obtained from the same transplant donor (N=19, median age 56 years (range: 18–80). Suspensions from homogenized organs were analyzed using a 35-marker mass cytometry panel and single-cell RNA sequencing (Figure A). B cells were also sorted for bulk BCR-sequencing.
The frequency of B cells within kidney CD45+ cells was lower than in spleen (8.8% vs. 26%, P<0.005). The renal cortex harbored ten times more B cells per gram of tissue than medulla. In contrast to spleen, B cell count and B:T cell ratio in renal cortex significantly increased with age (Figure B). Kidney B cells were enriched for non-naïve (CD27+IgD- and double-negative) subsets with innate-like characteristics when compared to spleen or younger donors. BCR analysis showed CDR3 repertoire differences between kidney and spleen, suggesting a specific antigenic exposure, but also clonotypes sharing between matched organs and across donors.
Our study shows that under homeostatic conditions, human kidneys harbor both antigen-experienced and innate-like B cells, mirroring studies of murine tissue-resident T cells. These cells expanded with age and showed a specific anatomical location to the outer part of the kidney, an area specialized for filtration of blood. These kidney B cells may play a role in local immune defense or contribute to immunopathology (autoimmunity, organ rejection), and further studies on diseased tissues and murine models are underway.