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6444695 
Journal Article 
The microanatomic segregation of selection by apoptosis in the germinal center 
Mayer, CT; Gazumyan, A; Kara, EE; Gitlin, AD; Golijanin, J; Viant, C; Pai, J; Oliveira, TY; Wang, Q; Escolano, A; Medina-Ramirez, M; Sanders, RW; Nussenzweig, MC 
2017 
1 
Science
ISSN: 0036-8075
EISSN: 1095-9203 
358 
6360 
n/a-n/a 
English 
28935768 
WOS:000412841500040 
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. 
; Receptors; Substrates; Compartments; Binding; Immune response; Cytidine deaminase; Indicators; Mutation; Homeostasis; Cell migration; Lymph nodes; Chromosome translocations; Point mutation; BCR protein; Immunization; T cell receptors; Cell death; Maturation; Immunoglobulins; Missense mutation; Apoptosis; Fluorescence; Affinity; Gene expression; Activation-induced cytidine deaminase; Lymphocytes B; Microscopy; Histology; Activation; Helper cells; Antibodies; Mice; B-cell receptor; Germinal centers; Genes; Genomes; Energy transfer; Cell proliferation; Clonal selection; Damage; Lymphocyte receptors; Cell division; Organs; Immunological memory; Nuclei; Fluorescence resonance energy transfer; Dendritic cells; Macrophages; Biology; Immune system/