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B 细胞亲和力成熟的主要限制是什么，我们可以通过疫苗接种诱导多少亲和力成熟？亲和力成熟是否是引发广泛保护的自我挫败过程？

What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Is Affinity Maturation a Self-Defeating Process for Eliciting Broad Protection?

机构信息

Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois 60637.

Committee on Immunology, The Knapp Center for Lupus and Immunology Research, The Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, Illinois 60637.

出版信息

Cold Spring Harb Perspect Biol. 2018 May 1;10(5):a028803. doi: 10.1101/cshperspect.a028803.

DOI:10.1101/cshperspect.a028803
PMID:28630076
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5899041/
Abstract

Vaccinations are one of the greatest success stories of modern medicine, saving millions of lives since their widespread adoption. However, several diseases continue to elude highly effective vaccination strategies. Chief among these are human immunodeficiency virus (HIV) and influenza (flu), both of which will require vaccines that can guide the creation of highly mutated, broadly neutralizing antibodies (bnAbs). The generation of bnAbs is hindered by our inability to effectively drive the high levels of affinity maturation required to achieve them in a large number of cells. Major limitations placed on affinity maturation derives from the inherent mutability of immunoglobulin genes, the evolved activation-induced cytidine deaminase (AID) targeting mechanisms that exist within them, and biases in targeting of particular epitope B cells.

摘要

疫苗接种是现代医学最伟大的成功故事之一，自从广泛采用以来，已经挽救了数百万人的生命。然而，仍有一些疾病难以通过高度有效的疫苗接种策略来预防。其中主要包括人类免疫缺陷病毒 (HIV) 和流感 (流感)，这两种疾病都需要能够引导产生高度突变、广泛中和抗体 (bnAb) 的疫苗。bnAb 的产生受到我们无法有效驱动大量细胞中所需的高亲和力成熟水平的限制。亲和力成熟的主要限制来自于免疫球蛋白基因的固有可变性、其中存在的进化激活诱导胞苷脱氨酶 (AID) 靶向机制，以及针对特定表位 B 细胞的靶向偏倚。