Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers

Hanover Matz, Richard S Taylor, Anthony K Redmond, Thomas M Hill, Rose Ruiz Daniels, Mariana Beltran, Neil C Henderson, Daniel J Macqueen, Helen Dooley

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The absence of germinal centers (GCs) in cartilaginous fishes lies at odds with data showing that nurse sharks can produce robust antigen-specific responses and affinity mature their B cell repertoires. To investigate this apparent incongruity, we performed RNA sequencing on single nuclei, allowing us to characterize the cell types present in the nurse shark spleen, and RNAscope to provide in situ cellular resolution of key marker gene expression following immunization with R-phycoerythrin (PE). We tracked PE to the splenic follicles where it co-localizes with CXCR5high centrocyte-like B cells and a population of putative T follicular helper (Tfh) cells, surrounded by a peripheral ring of Ki67+ AID+ CXCR4+ centroblast-like B cells. Further, we reveal selection of mutations in B cell clones dissected from these follicles. We propose that the B cell sites identified here represent the evolutionary foundation of GCs, dating back to the jawed vertebrate ancestor.

Original languageEnglish
Article number112664
Pages (from-to)1-16
Number of pages16
JournalCell Reports
Issue number7
Early online date20 Jun 2023
Publication statusPublished - 25 Jul 2023

Keywords / Materials (for Non-textual outputs)

  • B cells
  • CP: Immunology
  • T follicular helper cells
  • antibody
  • cartilaginous fish
  • evolution
  • germinal center
  • shark


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