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The microanatomic segregation of selection by apoptosis in the germinal center.

作者信息

Mayer Christian T, Gazumyan Anna, Kara Ervin E, Gitlin Alexander D, Golijanin Jovana, Viant Charlotte, Pai Joy, Oliveira Thiago Y, Wang Qiao, Escolano Amelia, Medina-Ramirez Max, Sanders Rogier W, Nussenzweig Michel C

机构信息

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.

出版信息

Science. 2017 Oct 13;358(6360). doi: 10.1126/science.aao2602. Epub 2017 Sep 21.


DOI:10.1126/science.aao2602
PMID:28935768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5957278/
Abstract

B cells undergo rapid cell division and affinity maturation in anatomically distinct sites in lymphoid organs called germinal centers (GCs). Homeostasis is maintained in part by B cell apoptosis. However, the precise contribution of apoptosis to GC biology and selection is not well defined. We developed apoptosis-indicator mice and used them to visualize, purify, and characterize dying GC B cells. Apoptosis is prevalent in the GC, with up to half of all GC B cells dying every 6 hours. Moreover, programmed cell death is differentially regulated in the light zone and the dark zone: Light-zone B cells die by default if they are not positively selected, whereas dark-zone cells die when their antigen receptors are damaged by activation-induced cytidine deaminase.

摘要

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本文引用的文献

[1]
The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells.

J Exp Med. 2017-3-6

[2]
The cell cycle restricts activation-induced cytidine deaminase activity to early G1.

J Exp Med. 2017-1

[3]
Sequencing and cloning of antigen-specific antibodies from mouse memory B cells.

Nat Protoc. 2016-10

[4]
Clonal redemption of autoantibodies by somatic hypermutation away from self-reactivity during human immunization.

J Exp Med. 2016-6-27

[5]
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.

Immunity. 2016-4-19

[6]
Visualizing antibody affinity maturation in germinal centers.

Science. 2016-3-4

[7]
A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens.

Nature. 2016-1-7

[8]
Sequence-Intrinsic Mechanisms that Target AID Mutational Outcomes on Antibody Genes.

Cell. 2015-11-12

[9]
Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma.

Cell. 2015-8-13

[10]
Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice.

Cell. 2015-6-18

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