Desikan, R and Antia, R and Dixit, NM (2021) Physical �strength� of the multi-protein chain connecting immune cells: Does the weakest link limit antibody affinity maturation?: The weakest link in the multi-protein chain facilitating antigen acquisition by B cells in germinal centres limits antibody affinity maturation. In: BioEssays . (In Press)
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Abstract
The affinities of antibodies (Abs) for their target antigens (Ags) gradually increase in vivo following an infection or vaccination, but reach saturation at values well below those realisable in vitro. This �affinity ceiling� could in many cases restrict our ability to fight infections and compromise vaccines. What determines the affinity ceiling has been an unresolved question for decades. Here, we argue that it arises from the strength of the chain of protein complexes that is pulled by B cells during the process of Ag acquisition. The affinity ceiling is determined by the strength of the weakest link in the chain. We identify the weakest link and show that the resulting affinity ceiling can explain the Ab affinities realized in vivo, providing a conceptual understanding of Ab affinity maturation. We explore plausible evolutionary underpinnings of the affinity ceiling, examine supporting evidence and alternative hypotheses and discuss implications for vaccination strategies. © 2021 Wiley Periodicals LLC
| Item Type: | Journal Article |
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| Publication: | BioEssays |
| Publisher: | John Wiley and Sons Inc |
| Additional Information: | Copyright to this article belongs to John Wiley and Sons Inc |
| Department/Centre: | Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering Division of Mechanical Sciences > Chemical Engineering |
| Date Deposited: | 08 Feb 2021 06:50 |
| Last Modified: | 08 Feb 2021 06:50 |
| URI: | http://eprints.iisc.ac.in/id/eprint/67864 |
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