Characterization of B-cell receptor clonality and immunoglobulin gene usage at multiple time points during active SARS-CoV-2 infection.

MedStar author(s):
Citation: Journal of Medical Virology. 95(10):e29179, 2023 10.PMID: 37877800Institution: MedStar Montgomery Medical Center | MedStar Union Memorial HospitalDepartment: HospitalistForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., IntramuralSubject headings: *COVID-19 | *Genes, Immunoglobulin | Antibodies, Viral | B-Lymphocytes | COVID-19/ge [Genetics] | Humans | Receptors, Antigen, B-Cell/ge [Genetics] | SARS-CoV-2/ge [Genetics]Year: 2023ISSN:
  • 0146-6615
Name of journal: Journal of medical virologyAbstract: Although monoclonal antibodies to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are known, B-cell receptor repertoire and its change in patients during coronavirus disease-2019 (COVID-19) progression is underreported. We aimed to study this molecularly. We used immunoglobulin heavy chain (IGH) variable region (IGHV) spectratyping and next-generation sequencing of peripheral blood B-cell genomic DNA collected at multiple time points during disease evolution to study B-cell response to SARS-CoV-2 infection in 14 individuals with acute COVID-19. We found a broad distribution of responding B-cell clones. The IGH gene usage was not significantly skewed but frequencies of individual IGH genes changed repeatedly. We found predominant usage of unmutated and low mutation-loaded IGHV rearrangements characterizing naive and extrafollicular B cells among the majority of expanded peripheral B-cell clonal lineages at most tested time points in most patients. IGH rearrangement usage showed no apparent relation to anti-SARS-CoV-2 antibody titers. Some patients demonstrated mono/oligoclonal populations carrying highly mutated IGHV rearrangements indicating antigen experience at some of the time points tested, including even before anti-SARS-CoV-2 antibodies were detected. We present evidence demonstrating that the B-cell response to SARS-CoV-2 is individual and includes different lineages of B cells at various time points during COVID-19 progression. Copyright Published 2023. This article is a U.S. Government work and is in the public domain in the USA.All authors: Arons E, Henry K, Haas C, Gould M, Tsintolas J, Mauter J, Zhou H, Burbelo PD, Cohen JI, Kreitman RJFiscal year: FY2024Digital Object Identifier: Date added to catalog: 2024-01-16
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Journal Article MedStar Authors Catalog Article 37877800 Available 37877800

Although monoclonal antibodies to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are known, B-cell receptor repertoire and its change in patients during coronavirus disease-2019 (COVID-19) progression is underreported. We aimed to study this molecularly. We used immunoglobulin heavy chain (IGH) variable region (IGHV) spectratyping and next-generation sequencing of peripheral blood B-cell genomic DNA collected at multiple time points during disease evolution to study B-cell response to SARS-CoV-2 infection in 14 individuals with acute COVID-19. We found a broad distribution of responding B-cell clones. The IGH gene usage was not significantly skewed but frequencies of individual IGH genes changed repeatedly. We found predominant usage of unmutated and low mutation-loaded IGHV rearrangements characterizing naive and extrafollicular B cells among the majority of expanded peripheral B-cell clonal lineages at most tested time points in most patients. IGH rearrangement usage showed no apparent relation to anti-SARS-CoV-2 antibody titers. Some patients demonstrated mono/oligoclonal populations carrying highly mutated IGHV rearrangements indicating antigen experience at some of the time points tested, including even before anti-SARS-CoV-2 antibodies were detected. We present evidence demonstrating that the B-cell response to SARS-CoV-2 is individual and includes different lineages of B cells at various time points during COVID-19 progression. Copyright Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

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