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. (14th January 2021)

• Record Type: Journal Article
• Authors: Desikan, Rajat; Antia, Rustom; Dixit, Narendra M.
• Is Part Of: BioEssays. Volume 43:Number 4(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-01-14
• Subjects: affinity ceiling -- antibody affinity maturation -- B cell -- Bell model -- evolution -- follicular dendritic cell -- germinal centre -- humoral immunity -- rupture force -- vaccine; Molecular biology -- Periodicals; Cytology -- Periodicals; Developmental biology -- Periodicals; 572.8
• DOI: 10.1002/bies.202000159
• Languages: English
• ISSNs: 0265-9247

Abstract

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. Abstract : Affinities of antibodies (Abs) for their target antigens (Ags) are far smaller in vivo than what can be realized in vitro. Here, we argue that the weakest link in the chain of protein complexes involved in Ag acquisition by germinal center B cells sets an affinity ceiling for Abs in vivo.