Naïve B-cell receptors specific for SARS-CoV-2 receptor-binding domain epitopes (Naïve SARS-CoV-2 RBD-specific BCRs)

Naïve B-cell receptors (BCRs) specific for SARS-CoV-2 receptor-binding domain (RBD) epitopes represent the initial recognition molecules of the humoral immune system for the virus. These receptors are membrane-bound immunoglobulins expressed on the surface of B cells that have not yet been activated by the SARS-CoV-2 antigen. They serve as the critical therapeutic target for vaccine development, where immunogens are designed to specifically bind and activate these precursors to trigger a protective immune response (Robbiani et al., 2020). The RBD is the primary focus because it contains the motifs necessary for binding the human ACE2 receptor, making it the most vulnerable site for neutralization (Greaney et al., 2021). In the human naïve repertoire, certain germline genes, such as IGHV3-53 and IGHV3-66, are frequently utilized to form these receptors due to their inherent structural compatibility with the RBD (Yuan et al., 2020). Upon interaction with a vaccine or viral antigen, these B cells enter germinal centers to undergo affinity maturation, leading to the production of high-affinity antibodies. Identifying the frequency and structural characteristics of these naïve BCRs is vital for germline-targeting vaccine strategies aimed at inducing broadly neutralizing antibodies against diverse sarbecoviruses (Stamatatos et al., 2021).

Other names

SARS-CoV-2 RBD-specific naïve B-cell receptorsGermline SARS-CoV-2 RBD-binding BCRsPrecursor B-cell receptors for SARS-CoV-2 neutralizing antibodiesNaïve B-cell receptors (BCRs)

Vaccine-derived antigens (immunogens) bind to these receptors on naïve B cells, initiating signal transduction and B-cell activation, which leads to clonal expansion, germinal center formation, and the eventual secretion of high-affinity neutralizing antibodies.