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Cell Rep ; 38(7): 110393, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1719435


B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies.

COVID-19/immunology , Receptors, Antigen, B-Cell/immunology , Vaccination , B-Lymphocytes/immunology , COVID-19/prevention & control , Clonal Evolution , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Immunoglobulin Isotypes/genetics , Immunoglobulin Isotypes/immunology , Immunoglobulin Variable Region/genetics , Immunoglobulin Variable Region/immunology , Kinetics , Receptors, Antigen, B-Cell/genetics , SARS-CoV-2/immunology , Severity of Illness Index , Somatic Hypermutation, Immunoglobulin/immunology , Spike Glycoprotein, Coronavirus/immunology