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

Citation

Matz H, Taylor RS, Redmond AK, Hill TM, Ruiz Daniels R, Beltran M, Henderson NC, Macqueen DJ & Dooley H (2023) Organized B cell sites in cartilaginous fishes reveal the evolutionary foundation of germinal centers. Cell Reports, 42 (7), Art. No.: 112664. https://doi.org/10.1016/j.celrep.2023.112664

Abstract
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.

Keywords
cartilaginous fish; shark; antibody; germinal center; B cells; T follicular helper cells; evolution

Notes
Gold

Journal
Cell Reports: Volume 42, Issue 7

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