Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the pandemic of coronavirus disease 2019 (COVID-19). Great international efforts have been put into the development of prophylactic vaccines and neutralizing antibodies. However, the knowledge about the B cell immune response induced by the SARS-CoV-2 virus is still limited. Here, we report a comprehensive characterization of the dynamics of immunoglobin heavy chain (IGH) repertoire in COVID-19 patients. By using next-generation sequencing technology, we examined the temporal changes in the landscape of the patient’s immunological status, and found dramatic changes in the IGH within the patients’ immune system after the onset of COVID-19 symptoms. Although different patients have distinct immune responses to SARS-CoV-2 infection, by employing clonotype overlap, lineage expansion and clonotype network analyses, we observed a higher clonotype overlap and substantial lineage expansion of B cell clones during 2-3 weeks of illness, which is of great importance to B-cell immune responses. Meanwhile, for preferences of V gene usage during SARS-CoV-2 infection, IGHV3-74 and IGHV4-34 and IGHV4-39 in COVID-19 patients were more abundant than that of healthy controls. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development as well as mechanistic research.

Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination

“…To be able to analyze individual maturation trajectories of B cells in the primary vaccination series versus upon third vaccination, we set out to identify developmental B lineages in all individual participants and to track them across the vaccination period. A B cell lineage is a group of clonotype-defined B cells that share a common V and J gene and a CDR3 sequence differing only in up to 10% of its amino acid positions (35). While we did not detect expanding B cell lineages in a substantial proportion of participants receiving their primary vaccination series, we found expanding lineages in the majority of patients receiving their third vaccination (Figure 5A).…”

“…We identified overlapping B cell lineages in the pre- and post-vaccination time point per patient. A B cell lineage was defined as a group of B cell clonotypes that share a common V and J gene and a CDR3 sequence differing only in up to 10% of its amino acid positions (35). Lineages and their evolution were visualised as stream plots with function plot.stacked from (https://www.r-bloggers.com/2013/12/data-mountains-and-streams-stacked-area-plots-in-r/).…”

Epitope profiling of coronavirus-binding antibodies using computational structural modelling

“…Despite this, the clonotypes found to be enriched/to bear similarity to CoV-AbDab antibodies post SARS-CoV-2 exposure often differ across studies (20)(21)(22). This may be partly due to the small sample sizes used in individual studies, and the intrinsic biases in individual VJ gene usage; Xiang et al found a larger variation between individuals within a cohort (healthy, or three different severities of COVID symptoms) than between cohorts (22). Another contributing factor is lineage clustering itself.…”