(A) Pipeline for antibody repertoire analysis. This study provided insights at the repertoire level for the B cell response after SARS-CoV-2 infection.ī cell receptor SARS-CoV-2 antibody repertoire isotype switching shared clonotype somatic hypermutation.Īnalysis of antibody response to SARS-CoV-2 infection. In this study, we analyzed the IgH transcripts and characterized the B cell clonal expansion and differentiation, isotype switching, and somatic hypermutation in COVID-19 patients. IMPORTANCE Although the canonical delineation of serum antibody responses following SARS-CoV-2 infection has been well established, the dynamics of antibody repertoire at the mRNA transcriptional level has not been well understood, especially the correlation between serum antibody titers and the antibody mRNA transcripts. Our analysis based on sequencing antibody repertoires from different individuals revealed key signatures of the systemic B cell response induced by SARS-CoV-2 infection. Furthermore, identical spike-specific IgH sequences were found in different COVID-19 patients, suggesting a highly convergent antibody response to SARS-CoV-2. These shared spike-specific IgH clusters are derived from the same lineage of several recently published neutralizing MAbs, including CC12.1, CC12.3, C102, REGN10977, and 4A8. By comparing the IgH repertoires that we sequenced with the 774 reported SARS-CoV-2-reactive monoclonal antibodies (MAbs), 13 shared spike-specific IgH clusters were found. Interestingly, 17 different IGHV germ line genes recombined with IGHJ6 showed significant clonal expansion. SARS-CoV-2 infection elicited poly-germ line reactive antibody responses. The antibody isotype switching landscape showed a transient IgA surge in the first week after symptom onset, followed by a sustained IgG elevation that lasted for at least 3 months. The proportion of low-SHM IgG clones strongly correlated with spike-specific IgG antibody titers, highlighting the significant activation of naive B cells in response to a novel virus infection. Massive clonal expansion of naive B cells with limited somatic hypermutation (SHM) was observed in the second week after symptom onset. To define the dynamics and characteristics of the antibody repertoire following SARS-CoV-2 infection, we analyzed the mRNA transcripts of immunoglobulin heavy chain (IgH) repertoires of 24 peripheral blood samples collected between 3 and 111 days after symptom onset from 10 COVID-19 patients. A comprehensive study of the B cell response against SARS-CoV-2 could be significant for understanding the immune response and developing therapeutical antibodies and vaccines.
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