A Model for Potential B-cell Precursors of Broadly Neutralizing HIV-1 Antibodies Selection and Antibody Affinity Maturation
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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 o...f nominal HIV-1 antigen and BCR interaction, may have implication for the vaccine designed and passive immunization. © 2019, Publicaciones Permanyer. All rights reserved.
Keywords:HIV-1 broadly neutralizing antibodies / Precursor of B-cell antigen receptor for broadly neutralizing antibodies / Toll-like receptor / Membrane proximal external region
Source:Aids Reviews, 2019, 21, 1, 23-27
ISSN: 1139-6121 (print); 1698-6997 (electronic)