Organized B Cell Sites in Cartilaginous Fishes Reveal the Evolutionary Foundation of Germinal Centers
Overview
Cell Biology
Molecular Biology
Authors
Affiliations
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 CXCR5 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.
Understanding vertebrate immunity through comparative immunology.
Boehm T Nat Rev Immunol. 2024; 25(2):141-152.
PMID: 39317775 DOI: 10.1038/s41577-024-01083-9.
Wang H, Chen J, Li Y, Zhang X, Liu X, Lu Y Nat Commun. 2024; 15(1):7627.
PMID: 39227568 PMC: 11372145. DOI: 10.1038/s41467-024-51761-4.
Hu C, Zhang N, Hong Y, Tie R, Fan D, Lin A Elife. 2024; 13.
PMID: 38497789 PMC: 10948150. DOI: 10.7554/eLife.92424.
CD4 and LAG-3 from sharks to humans: related molecules with motifs for opposing functions.
Takizawa F, Hashimoto K, Miyazawa R, Ohta Y, Verissimo A, Flajnik M Front Immunol. 2024; 14:1267743.
PMID: 38187381 PMC: 10768021. DOI: 10.3389/fimmu.2023.1267743.
Cold-blooded vertebrates evolved organized germinal center-like structures.
Shibasaki Y, Afanasyev S, Fernandez-Montero A, Ding Y, Watanabe S, Takizawa F Sci Immunol. 2023; 8(90):eadf1627.
PMID: 37910630 PMC: 11152321. DOI: 10.1126/sciimmunol.adf1627.