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

doi:10.1016/j.isci.2023.108496

Atypical B cells consist of subsets with distinct functional profiles

iScience. 2023 Nov 20;26(12):108496. doi: 10.1016/j.isci.2023.108496. eCollection 2023 Dec 15.

Authors

Raphael A Reyes¹, Gayani Batugedara¹, Paramita Dutta², Ashley B Reers¹, Rolando Garza¹, Isaac Ssewanyana^{3

4}, Prasanna Jagannathan^{5

6}, Margaret E Feeney^{7

8}, Bryan Greenhouse⁷, Sebastiaan Bol¹, Ferhat Ay^{2

9}, Evelien M Bunnik¹

Affiliations

¹ 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.
² Centers for Cancer Immunotherapy and Autoimmunity, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
³ Infectious Disease Research Collaboration, Kampala, Uganda.
⁴ Department of Infection Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
⁵ Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA 94305, USA.
⁶ Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA.
⁷ Department of Medicine, University of California, San Francisco, San Francisco, CA 94110, USA.
⁸ Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94110, USA.
⁹ Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.

Abstract

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.

Keywords: Biological sciences; Components of the immune system; Immunology; Parasitology; Transcriptomics.

Abstract

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