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The magnitude of germinal center reactions is restricted by a fixed number of preexisting niches

Item Type:Article
Title:The magnitude of germinal center reactions is restricted by a fixed number of preexisting niches
Creators Name:Avancena, P. and Song, T. and Yao, Y. and Fehlner-Peach, H. and Diamond, B. and Gu, H. and Rajewsky, K. and Zou, Y.R.
Abstract:Antibody affinity maturation occurs in the germinal center (GC), a highly dynamic structure that arises upon antigen stimulation and recedes after infection is resolved. While the magnitude of the GC reaction is highly fluctuating and depends on antigens or pathological conditions, it is unclear whether GCs are assembled ad hoc in different locations or in preexisting niches within B cell follicles. We show that follicular dendritic cells (FDCs), the essential cellular components of the GC architecture, form a predetermined number of clusters. The total number of FDC clusters is the same on several different genetic backgrounds and is not altered by immunization or inflammatory conditions. In unimmunized and germ-free mice, a few FDC clusters contain GC B cells; in contrast, immunization or autoimmune milieu significantly increases the frequency of FDC clusters occupied by GC B cells. Excessive occupancy of GC niches by GC B cells after repeated immunizations or in autoimmune conditions suppresses subsequent antibody responses to new antigens. These data indicate that the magnitude of the GC reaction is restricted by a fixed number of permissive GC niches containing preassembled FDC clusters. This finding may help in the future design of vaccination strategies and in the modulation of antibody-mediated autoimmunity.
Keywords:GC Niches, GC Response, Vaccination, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences
Volume:118
Number:30
Page Range:e2100576118
Date:27 July 2021
Official Publication:https://doi.org/10.1073/pnas.2100576118
PubMed:View item in PubMed

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