Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2

Abstract

<jats:p>During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.</jats:p>

Reinfection with SARS-CoV-2 and Failure of Humoral Immunity: a case report

“…Healthy human peripheral blood shows a predominance of naïve B cells expressing IgM and IgD without somatic hypermutation, and memory B cells with mutated class-switched antibodies. In contrast, the acute response to primary SARS-CoV-2 infection features large polyclonal expansions of recently class-switched, low somatic hypermutation B cells expressing IgG subclasses and, to a lesser degree, IgA subclasses, 19 as shown in longitudinal samples from an unrelated patient at day 9 (prior to seroconversion) and day 13 (after seroconversion) after primary infection with SARS-CoV-2. In contrast, clones with low somatic hypermutation did not emerge by day 14 or 18 after reinfection in patient InCoV139 ( Figure 4A ).…”

“…13 Functional nAbs were measured with a cell-culture based assay using pseudoviruses containing either the D614 or the G614 epitopes in spike. 21 Immunoglobulin heavy chain (IGH) genes expressed by peripheral blood B cells were sequenced with amplicon libraries produced for each isotype, 19 and paired IGH and light chain sequences were determined with single B cell transcriptome analysis. 19 All assays are described in depth (Supplemental Methods).…”

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

“…Severe disease was associated with earlier generation of anti-SARS-CoV-2 antibody, and peak neutralizing antibody was measured at approximately 2 ½ weeks. Stereotypic antibody responses to SARS-CoV-2 led to hypotheses that there should be cross-reactivity with SARS-CoV in the constant RBD [32]. In both humans and animals, such cross-reactivity was suspected to be due to non-neutralizing anti-S antibody again likely relating to a conserved region [33].…”

The adaptive immune receptor repertoire community as a model for FAIR stewardship of big immunology data

“… Montague et al [ 25 ] Preprint Ab/BCR 19 COVID-19 patients of varying disease severities Peripheral Blood samples 18.9 Expanded rare clonal lineages shared among patients; V-gene specific responses are highly individualized; longer CDRH3 lengths in Abs from patients with moderate and severe symptoms. Nielsen et al [ 26 ] Published Ab/BCR Admitted patients with symptoms of COVID-19 and confirmed SARSCoV infection by RT-qPCR Peripheral Blood samples 8.9 B cells utilized a limited subset of V genes, and extensive activation of IgG and IgA B cells without significant somatic mutation; expansion of B-cell clones as well as Abs with highly similar sequences shared among patients. Liao et al [ 27 ] Published TCR 12 COVID-19 patients of varying disease severities Bronchoalveolar lavage fluid 66.9 Greater clonal expansion of T cell clones in moderate disease than severe disease.…”