Diversification of the VH3-53 immunoglobulin gene segment by somatic hypermutation results in neutralization of SARS-CoV-2 virus variants
Bruhn M, Obara M, Salam A, Costa B, Ziegler A, Waltl I, Pavlou A, Hoffmann M, Graalmann T, Pöhlmann S, Schambach A, Kalinke U
Published in
European Journal of Immunology: Volume 54, Issue 7, Page e2451056
Abstract
COVID-19 induces re-circulating long-lived memory B cells (MBC) that, upon re-encounter with the pathogen, are induced to mount immunoglobulin responses. During convalescence, antibodies are subjected to affinity maturation, which enhances the antibody binding strength and generates new specificities that neutralize virus variants. Here, we performed a single-cell RNA sequencing analysis of spike-specific B cells from a SARS-CoV-2 convalescent subject. After COVID-19 vaccination, matured infection-induced MBC underwent recall and differentiated into plasmablasts. Furthermore, the transcriptomic profiles of newly activated B cells transiently shifted toward the ones of atypical and CXCR3(+) B cells and several B-cell clonotypes massively expanded. We expressed monoclonal antibodies (mAbs) from all B-cell clones from the largest clonotype that used the VH3-53 gene segment. The in vitro analysis revealed that some somatic hypermutations enhanced the neutralization breadth of mAbs in a putatively stochastic manner. Thus, somatic hypermutation of B-cell clonotypes generates an anticipatory memory that can neutralize new virus variants.
Open in PubMedAuthors

Dr. Dr. Theresa Graalmann
Junior Group Leader

Dr. Annett Ziegler
Postdoctoral Researcher

Dr. Matthias Bruhn
Postdoctoral Researcher

Maureen Obara
PhD Student (ZIB Program)

Dr. Andreas Pavlou
Postdoctoral Researcher

Abdus Salam
PhD Student

Prof. Dr. Ulrich Kalinke
Executive Director

Dr. Inken Waltl
Postdoctoral Researcher