Naïve B-cell receptor specific for SARS-CoV-2 spike protein epitopes (Naïve SARS-CoV-2 spike BCR)

Naïve B-cell receptors (BCRs) specific for SARS-CoV-2 spike epitopes are the primary sensors on B cells that recognize the virus before an immune response is established. These receptors are membrane-bound immunoglobulins that have not yet undergone somatic hypermutation or class-switch recombination. Research has shown that the human naïve repertoire contains specific germline gene sequences, such as IGHV3-53, that are predisposed to binding the SARS-CoV-2 receptor-binding domain (RBD) (Yuan et al., 2020, Science). In vaccine development, these BCRs are considered therapeutic targets for germline-targeting strategies, which use engineered immunogens to selectively activate B cells with the potential to develop into broadly neutralizing antibodies (Stamatatos et al., 2021, Science). When a vaccine antigen binds to these naïve BCRs, it triggers a signaling cascade that leads to B-cell activation and the formation of germinal centers. Within these centers, the B cells undergo affinity maturation to increase their binding strength to the spike protein. This process is essential for generating protective immunity against COVID-19 and its variants (Sakharkar et al., 2021, Nature Communications). However, the low precursor frequency of these specific BCRs in some individuals can pose a challenge for achieving uniform vaccine efficacy. Furthermore, ensuring that these receptors mature into neutralizing rather than non-neutralizing antibodies is a key focus of current immunological research.

Other names

Germline B-cell receptorSARS-CoV-2 spike-specific naïve BCRPrecursor B-cell receptor for SARS-CoV-2Naïve B-cell receptor specific for SARS-CoV-2 spike epitopes

Binding of vaccine-derived antigens or engineered immunogens to the naïve B-cell receptor triggers signal transduction, leading to B-cell expansion and affinity maturation within germinal centers.