A Model for Potential B-cell Precursors of Broadly Neutralizing HIV-1 Antibodies Selection and Antibody Affinity Maturation.

The goal of this report was to propose a model, wherein synergy between the B-cell antigen receptor (BCR) and toll-like receptor (TLR) signaling is involved in the selection of the B-cell precursors of HIV-1 broadly neutralizing antibodies (bnAbs) with long heavy chain complementarity determining regions 3, from immature/transitional B cells. The model predicts the involvement of Ab/HIV-1 complexes in a way that Ab from the complex binds both BCRs and HIV-1, while on internalization of HIV-1 TLR ligands such as CpG motifs interacts with TLR9. The result of BCR and TLR9 orchestrated signaling is a formation of somatically mutated memory B cells potential precursors of bnAbs. Generated memory B cells continuously exposed to different Ab/HIV-1 complexes can elicit specific bnAb by stochastic somatic hypermutation rather than in the Darwinian process. This new view of the interaction between Ab/HIV-1 complexes and immune system, leading to affinity maturation of the bnAbs in the absence of nominal HIV-1 antigen and BCR interaction, may have implication for the vaccine designed and passive immunization.