Atypical B cells consist of subsets with distinct functional profiles
Raphael A. Reyes,
Gayani Batugedara,
Paramita Dutta,
Ashley B. Reers,
Rolando Garza,
Isaac Ssewanyana,
Prasanna Jagannathan,
Margaret E. Feeney,
Bryan Greenhouse,
Sebastiaan Bol,
Ferhat Ay,
Evelien M. Bunnik
Affiliations
Raphael A. Reyes
Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Gayani Batugedara
Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Paramita Dutta
Centers for Cancer Immunotherapy and Autoimmunity, La Jolla Institute for Immunology, La Jolla, CA 92037, USA
Ashley B. Reers
Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Rolando Garza
Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Isaac Ssewanyana
Infectious Disease Research Collaboration, Kampala, Uganda; Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
Prasanna Jagannathan
Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA
Margaret E. Feeney
Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94110, USA
Bryan Greenhouse
Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA
Sebastiaan Bol
Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
Ferhat Ay
Centers for Cancer Immunotherapy and Autoimmunity, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA
Evelien M. Bunnik
Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Corresponding author
Summary: Atypical B cells are a population of activated B cells that are commonly enriched in individuals with chronic immune activation but are also part of a normal immune response to infection or vaccination. To better define the role of atypical B cells in the human adaptive immune response, we performed single-cell sequencing of transcriptomes, cell surface markers, and B cell receptors in individuals with chronic exposure to the malaria parasite Plasmodium falciparum, a condition known to lead to accumulation of circulating atypical B cells. We identified three previously uncharacterized populations of atypical B cells with distinct transcriptional and functional profiles and observed marked differences among these three subsets in their ability to produce immunoglobulin G upon T-cell-dependent activation. Our findings help explain the conflicting observations in prior studies regarding the function of atypical B cells and highlight their different roles in the adaptive immune response in chronic inflammatory conditions.
