B 细胞亲和力成熟的主要限制是什么，我们可以通过接种疫苗驱动多少亲和力成熟？来自 HIV-1 抗体反应的教训。
What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Lessons from the Antibody Response to HIV-1.
机构信息
Laboratory of Lymphocyte Dynamics, The Rockefeller University, New York, New York 10065.
Laboratory of Humoral Response to Pathogens, Institut Pasteur, Paris 75015, France.
出版信息
Cold Spring Harb Perspect Biol. 2018 May 1;10(5):a029389. doi: 10.1101/cshperspect.a029389.
Abstract
Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.
摘要
大多数广谱中和抗体对 HIV-1 具有一个共同点，那就是极高程度的体细胞超突变（SHM），这与其中和多种病毒株的能力相关。然而，通过免疫接种实现这种极端的 SHM 仍然是一个挑战。在这里，我们讨论了 HIV-1 感染期间的抗原变异如何通过允许生发中心中的多次亲和力成熟迭代循环来加剧 SHM，并推测了如何通过疫苗接种来重现这一过程。
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本文引用的文献
1
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2
Germinal Center B Cell Dynamics.生发中心B细胞动力学
Immunity. 2016 Sep 20;45(3):471-482. doi: 10.1016/j.immuni.2016.09.001.
3
Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires.在具有不同前体库的小鼠中诱导HIV中和抗体谱系
Cell. 2016 Sep 8;166(6):1471-1484.e18. doi: 10.1016/j.cell.2016.07.029.
4
Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies.定制免疫原引导亲和力成熟以产生HIV中和抗体。
Cell. 2016 Sep 8;166(6):1459-1470.e11. doi: 10.1016/j.cell.2016.08.005.
5
Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice.序贯免疫在Ig基因敲入小鼠中引发广泛中和性抗HIV-1抗体。
Cell. 2016 Sep 8;166(6):1445-1458.e12. doi: 10.1016/j.cell.2016.07.030.
6
Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections.宿主-病原体协同进化与慢性感染中广泛中和抗体的出现
PLoS Genet. 2016 Jul 21;12(7):e1006171. doi: 10.1371/journal.pgen.1006171. eCollection 2016 Jul.
7
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8
Regulated selection of germinal-center cells into the memory B cell compartment.生发中心细胞向记忆 B 细胞池的受控选择。
Nat Immunol. 2016 Jul;17(7):861-9. doi: 10.1038/ni.3460. Epub 2016 May 9.
9
Complex Antigens Drive Permissive Clonal Selection in Germinal Centers.复杂抗原驱动生发中心的许可性克隆选择。
Immunity. 2016 Mar 15;44(3):542-552. doi: 10.1016/j.immuni.2016.02.010. Epub 2016 Mar 3.
10
Visualizing antibody affinity maturation in germinal centers.可视化生发中心中的抗体亲和力成熟过程。
Science. 2016 Mar 4;351(6277):1048-54. doi: 10.1126/science.aad3439. Epub 2016 Feb 18.
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