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

Abstract

AbstractAlthough 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 naïve 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.