Naïve B-cell receptor (BCR)

Naïve B-cell receptors (BCRs) are membrane-bound immunoglobulins found on the surface of B cells that have not yet encountered their specific antigen. In modern vaccine development, particularly for HIV-1, these receptors are targeted by germline-targeting immunogens designed to trigger the development of broadly neutralizing antibodies (bNAbs) (Jardine et al., 2016, Science). These vaccines, such as the eOD-GT8 60mer, are engineered to bind with high affinity to rare naïve BCRs that possess the genetic potential to evolve into protective antibodies (Leggat et al., 2022, Science). Upon binding, the BCR initiates a signaling cascade that leads to B-cell activation, proliferation, and entry into germinal centers for somatic hypermutation. This targeted approach aims to overcome the challenges of traditional vaccination by guiding the immune system through a specific evolutionary pathway to produce antibodies capable of neutralizing diverse viral strains (IAVI, 2021). Monitoring the frequency and response of these specific naïve BCRs is critical for evaluating the efficacy of next-generation vaccine candidates.

Other names

Germline B-cell receptorNaïve BCRAntigen-specific B-cell receptorB-cell antigen receptor

Germline-targeting immunogens bind to and cross-link specific naïve B-cell receptors to initiate B-cell activation, clonal expansion, and the affinity maturation process required to generate broadly neutralizing antibodies.