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Antibody Repertoire and Gene Expression Dynamics of Diverse Human B Cell States During Affinity Maturation

33 Pages Posted: 16 Jun 2020 Sneak Peek Status: Under Review

See all articles by Hamish William King

Hamish William King

Queen Mary University of London - Centre for Immunobiology

Nara Orban

The Royal London Hospital - Barts Health Ear, Nose and Throat Service

John C. Riches

Queen Mary University of London - Centre for Haemato-Oncology

Andrew J. Clear

Queen Mary University of London - Centre for Haemato-Oncology

Gary Warnes

Queen Mary University of London - Flow Cytometry Core Facility

Sarah A. Teichmann

Wellcome Genome Campus - Wellcome Sanger Institute

Louisa K. James

Queen Mary University of London - Centre for Immunobiology

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Abstract

In response to antigen challenge, B cells clonally expand, undergo selection and differentiate to produce mature B cell subsets and high affinity antibodies. However, the interplay between dynamic B cell states and their antibody-based selection is challenging to decipher in primary human tissue. We have applied an integrated analysis of bulk and single-cell antibody repertoires paired with single-cell transcriptomics of human B cells undergoing affinity maturation. We define unique gene expression and antibody repertoires of known and novel B cell states, including a pre-germinal centre state primed to undergo class switch recombination. We dissect antibody class-dependent gene expression of germinal centre and memory B cells to find that class switching prior to germinal centre entry dictates the capacity of B cells to undergo antibody-based selection and differentiate. Together, our analyses provide unprecedented resolution into the gene expression and selection dynamics that shape B cell-mediated immunity.

Keywords: antibody, repertoire, B cell, germinal centre, affinity maturation, single-cell genomics, human immunology

Suggested Citation

King, Hamish William and Orban, Nara and Riches, John C. and Clear, Andrew J. and Warnes, Gary and Teichmann, Sarah A. and James, Louisa K., Antibody Repertoire and Gene Expression Dynamics of Diverse Human B Cell States During Affinity Maturation. Available at SSRN: https://ssrn.com/abstract=3608389 or http://dx.doi.org/10.2139/ssrn.3608389
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Hamish William King

Queen Mary University of London - Centre for Immunobiology

Mile End Rd
Mile End Road
London, E1 4NS
United Kingdom

Nara Orban

The Royal London Hospital - Barts Health Ear, Nose and Throat Service

Whitechapel Road
London, E1 1BB
United Kingdom

John C. Riches

Queen Mary University of London - Centre for Haemato-Oncology

Mile End Rd
Mile End Road
London, London E1 4NS
United Kingdom

Andrew J. Clear

Queen Mary University of London - Centre for Haemato-Oncology

Mile End Rd
Mile End Road
London, London E1 4NS
United Kingdom

Gary Warnes

Queen Mary University of London - Flow Cytometry Core Facility

Mile End Rd
Mile End Road
London, London E1 4NS
United Kingdom

Sarah A. Teichmann

Wellcome Genome Campus - Wellcome Sanger Institute

Hinxton
Cambridge, England CB10 1SA
United Kingdom

Louisa K. James (Contact Author)

Queen Mary University of London - Centre for Immunobiology ( email )

United Kingdom

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