Cell Reports (Feb 2021)
Atypical B cells are part of an alternative lineage of B cells that participates in responses to vaccination and infection in humans
- Henry J. Sutton,
- Racheal Aye,
- Azza H. Idris,
- Rachel Vistein,
- Eunice Nduati,
- Oscar Kai,
- Jedida Mwacharo,
- Xi Li,
- Xin Gao,
- T. Daniel Andrews,
- Marios Koutsakos,
- Thi H.O. Nguyen,
- Maxim Nekrasov,
- Peter Milburn,
- Auda Eltahla,
- Andrea A. Berry,
- Natasha KC,
- Sumana Chakravarty,
- B. Kim Lee Sim,
- Adam K. Wheatley,
- Stephen J. Kent,
- Stephen L. Hoffman,
- Kirsten E. Lyke,
- Philip Bejon,
- Fabio Luciani,
- Katherine Kedzierska,
- Robert A. Seder,
- Francis M. Ndungu,
- Ian A. Cockburn
Affiliations
- Henry J. Sutton
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
- Racheal Aye
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia; KEMRI - Wellcome Research Programme/Centre for Geographical Medicine Research (Coast), Kilifi, Kenya
- Azza H. Idris
- Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA
- Rachel Vistein
- Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA
- Eunice Nduati
- KEMRI - Wellcome Research Programme/Centre for Geographical Medicine Research (Coast), Kilifi, Kenya; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
- Oscar Kai
- KEMRI - Wellcome Research Programme/Centre for Geographical Medicine Research (Coast), Kilifi, Kenya
- Jedida Mwacharo
- KEMRI - Wellcome Research Programme/Centre for Geographical Medicine Research (Coast), Kilifi, Kenya
- Xi Li
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
- Xin Gao
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
- T. Daniel Andrews
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
- Marios Koutsakos
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC 3000, Australia
- Thi H.O. Nguyen
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC 3000, Australia
- Maxim Nekrasov
- Australian Cancer Research Foundation Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
- Peter Milburn
- Australian Cancer Research Foundation Biomolecular Resource Facility, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
- Auda Eltahla
- School of Medical Science, Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Andrea A. Berry
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Natasha KC
- Sanaria Inc., Rockville, MD 20850, USA
- Sumana Chakravarty
- Sanaria Inc., Rockville, MD 20850, USA
- B. Kim Lee Sim
- Sanaria Inc., Rockville, MD 20850, USA
- Adam K. Wheatley
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC 3000, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, VIC, Australia
- Stephen J. Kent
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC 3000, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, VIC, Australia
- Stephen L. Hoffman
- Sanaria Inc., Rockville, MD 20850, USA
- Kirsten E. Lyke
- Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
- Philip Bejon
- KEMRI - Wellcome Research Programme/Centre for Geographical Medicine Research (Coast), Kilifi, Kenya; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
- Fabio Luciani
- School of Medical Science, Kirby Institute, University of New South Wales, Sydney, NSW 2052, Australia
- Katherine Kedzierska
- Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Melbourne, VIC 3000, Australia
- Robert A. Seder
- Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA
- Francis M. Ndungu
- KEMRI - Wellcome Research Programme/Centre for Geographical Medicine Research (Coast), Kilifi, Kenya; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, UK
- Ian A. Cockburn
- Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia; Corresponding author
- Journal volume & issue
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Vol. 34,
no. 6
p. 108684
Abstract
Summary: The diversity of circulating human B cells is unknown. We use single-cell RNA sequencing (RNA-seq) to examine the diversity of both antigen-specific and total B cells in healthy subjects and malaria-exposed individuals. This reveals two B cell lineages: a classical lineage of activated and resting memory B cells and an alternative lineage, which includes previously described atypical B cells. Although atypical B cells have previously been associated with disease states, the alternative lineage is common in healthy controls, as well as malaria-exposed individuals. We further track Plasmodium-specific B cells after malaria vaccination in naive volunteers. We find that alternative lineage cells are primed after the initial immunization and respond to booster doses. However, alternative lineage cells develop an atypical phenotype with repeated boosts. The data highlight that atypical cells are part of a wider alternative lineage of B cells that are a normal component of healthy immune responses.
