1. Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures
- Author
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Jacob D. Galson, Sebastian Schaetzle, Rachael J. M. Bashford-Rogers, Matthew I. J. Raybould, Aleksandr Kovaltsuk, Gavin J. Kilpatrick, Ralph Minter, Donna K. Finch, Jorge Dias, Louisa K. James, Gavin Thomas, Wing-Yiu Jason Lee, Jason Betley, Olivia Cavlan, Alex Leech, Charlotte M. Deane, Joan Seoane, Carlos Caldas, Daniel J. Pennington, Paul Pfeffer, Jane Osbourn, Caldas, Carlos [0000-0003-3547-1489], Apollo - University of Cambridge Repository, Institut Català de la Salut, [Galson JD, Schaetzle S, Kilpatrick GJ] Alchemab Therapeutics Ltd, London, United Kingdom. [Bashford-Rogers RJM] Alchemab Therapeutics Ltd, London, United Kingdom. Wellcome Centre for Human Genetics, Oxford, United Kingdom. [Raybould MIJ, Kovaltsuk A] Oxford Protein Informatics Group, Department of Statistics, University of Oxford, Oxford, United Kingdom. [Seoane J] Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
0301 basic medicine ,Male ,Antibodies, Viral ,COVID-19 (Malaltia) ,0302 clinical medicine ,antibody ,virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES] ,Bystander effect ,Immunology and Allergy ,Original Research ,education.field_of_study ,B-Lymphocytes ,aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::globulinas séricas::inmunoglobulinas::receptores de antígenos de linfocitos B [COMPUESTOS QUÍMICOS Y DROGAS] ,biology ,breakpoint cluster region ,High-Throughput Nucleotide Sequencing ,Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES] ,Middle Aged ,BCR ,Vaccination ,Investigative Techniques::Genetic Techniques::Sequence Analysis [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,medicine.anatomical_structure ,B-cell repertoire ,Spike Glycoprotein, Coronavirus ,Female ,Antibody ,lcsh:Immunologic diseases. Allergy ,Population ,B-cell receptor ,Immunology ,Receptors, Antigen, B-Cell ,Computational biology ,Deep sequencing ,03 medical and health sciences ,Immune system ,Lymphopenia ,Homologous chromosome ,medicine ,Humans ,education ,B cell ,Seqüència de nucleòtids ,Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Serum Globulins::Immunoglobulins::Receptors, Antigen, B-Cell [CHEMICALS AND DRUGS] ,convergence ,SARS-CoV-2 ,FOS: Clinical medicine ,COVID-19 ,Antibodies, Neutralizing ,técnicas de investigación::técnicas genéticas::análisis de secuencias [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,030104 developmental biology ,biology.protein ,lcsh:RC581-607 ,Antígens - Receptors ,030217 neurology & neurosurgery - Abstract
Repertori de cèl·lules B; SARS-CoV-2; Anticòs Repertorio de células B; SARS-CoV-2; Anticuerpo B-cell repertoire; SARS-CoV-2; Antibody Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses. MR is supported by an Engineering and Physical Sciences Research Council (EPSRC) and Medical Research Council (MRC) grant (EP/L016044/1). AK is supported by a Biotechnology and Biological Sciences Research Council (BBSRC) grant (BB/M011224/1).
- Published
- 2020