Department of Chemical Engineering, Indian Institute of Science, Bengaluru, India.
Department of Biology, Emory University, Atlanta, Georgia, USA.
Bioessays. 2021 Apr;43(4):e2000159. doi: 10.1002/bies.202000159. Epub 2021 Jan 14.
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.
抗体（Abs）与目标抗原（Ags）的亲和力在感染或接种疫苗后会在体内逐渐升高，但达到的饱和度远低于体外可实现的水平。这种“亲和力天花板”在许多情况下可能会限制我们对抗感染的能力并影响疫苗的效果。数十年来，决定亲和力天花板的因素一直是一个悬而未决的问题。在这里，我们认为它源于 B 细胞在获取抗原过程中拉动的蛋白质复合物链的强度。亲和力天花板取决于链条中最薄弱的环节的强度。我们确定了最薄弱的环节，并表明由此产生的亲和力天花板可以解释体内实现的 Ab 亲和力，为 Ab 亲和力成熟提供了概念性的理解。我们探讨了亲和力天花板的可能进化基础，检验了支持性证据和替代假设，并讨论了对疫苗接种策略的影响。
