CD62L expression marks a functionally distinct subset of memory B cells
Christopher H. Hanson,
Brittany Henry,
Pradhnesh Andhare,
Frank J. Lin,
Haley Pak,
Jackson S. Turner,
Lucas J. Adams,
Tom Liu,
Daved H. Fremont,
Ali H. Ellebedy,
Brian J. Laidlaw
Affiliations
Christopher H. Hanson
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Brittany Henry
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Pradhnesh Andhare
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Frank J. Lin
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Haley Pak
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Jackson S. Turner
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Lucas J. Adams
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
Tom Liu
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA
Daved H. Fremont
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO, USA
Ali H. Ellebedy
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology & Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA; Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, Saint Louis, MO, USA
Brian J. Laidlaw
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Corresponding author
Summary: The memory B cell response consists of phenotypically distinct subsets that differ in their ability to respond upon antigen re-encounter. However, the pathways regulating the development and function of memory B cell subsets are poorly understood. Here, we show that CD62L and CD44 are progressively expressed on mouse memory B cells and identify transcriptionally and functionally distinct memory B cell subsets. Bcl6 is important in regulating memory B cell subset differentiation with overexpression of Bcl6 resulting in impaired CD62L+ memory B cell development. Bcl6 regulates memory B cell subset development through control of a network of genes, including Bcl2 and Zeb2. Overexpression of Zeb2 impairs the development of CD62L+ memory B cells. Importantly, CD62L is also differentially expressed on human memory B cells following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and identifies phenotypically distinct populations. Together, these data indicate that CD62L expression marks functionally distinct memory B cell subsets.
