Journal article

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 HO Nguyen, Maxim Nekrasov, Peter Milburn, Auda Eltahla, Andrea A Berry, KC Natasha, Sumana Chakravarty, B Kim Lee Sim, Adam K Wheatley Show all

Cell Reports | CELL PRESS | Published : 2021

Abstract

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..

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Grants

Awarded by National Health and Medical Research Council


Awarded by National Institute of Allergy and Infectious Diseases Small Business Innovation Research Grants


Awarded by MRC/DFID African Research Leadership Award


Awarded by European and Developing Countries Clinical Trial Partnership


Awarded by African Academy of Sciences through the DELTAS Africa Initiative


Funding Acknowledgements

We would like to thank the University of Maryland study volunteers from malaria clinical trial VRC314. We are grateful to the KEMRI/CGMRC field team for their dedication in the recruitments, malaria surveillance data, and sample collection and the laboratory team that processed the samples. We are also indebted to the study participants. We would like to thank Harpreet Vohra and Michael Devoy of the Imaging and Cytometry Facility at the Australian National University for assistance with flow cytometry and sorting. This work was supported by National Health and Medical Research Council project grant support to I.A.C. (GNT1158404). Production and characterization of PfSPZ vaccine were supported in part by National Institute of Allergy and Infectious Diseases Small Business Innovation Research Grants 5R44AI055229-11 (to S.L.H.), 5R44AI058499-08 (to S.L.H.), and 5R44AI058375-08 (to S.L.H.). F.M.N. was supported by an MRC/DFID African Research Leadership Award (MR/P020321/1) and a Senior Fellowship from the European and Developing Countries Clinical Trial Partnership (TMA2016SF-1513). R.A. was supported by the African Academy of Sciences through the DELTAS Africa Initiative (DEL-15-003).