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
Affiliations
Hanover Matz
Department of Microbiology and Immunology, University of Maryland School of Medicine, Institute of Marine and Environmental Technology, Baltimore, MD, USA
Richard S. Taylor
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
Anthony K. Redmond
Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland
Thomas M. Hill
Department of Microbiology and Immunology, University of Maryland School of Medicine, Institute of Marine and Environmental Technology, Baltimore, MD, USA
Rose Ruiz Daniels
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
Mariana Beltran
Centre for Inflammation Research, The Queen’s Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK
Neil C. Henderson
Centre for Inflammation Research, The Queen’s Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
Daniel J. Macqueen
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh, UK
Helen Dooley
Department of Microbiology and Immunology, University of Maryland School of Medicine, Institute of Marine and Environmental Technology, Baltimore, MD, USA; Corresponding author
Summary: 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.
