期刊
NATURE IMMUNOLOGY
卷 17, 期 7, 页码 870-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3458
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资金
- European Research Council [648228]
- EMBO Young Investigator Programme
- Francis Crick Institute from Cancer Research UK
- Francis Crick Institute from UK Medical Research Council
- Francis Crick Institute from Wellcome Trust
- European Research Council (ERC) [648228] Funding Source: European Research Council (ERC)
- MRC [MC_U117597138] Funding Source: UKRI
- Medical Research Council [1226960, MC_U117597138] Funding Source: researchfish
- The Francis Crick Institute [10185] Funding Source: researchfish
B cell activation is regulated by B cell antigen receptor (BCR) signaling and antigen internalization in immune synapses. Using large-scale imaging across B cell subsets, we found that, in contrast with naive and memory B cells, which gathered antigen toward the synapse center before internalization, germinal center (GC) B cells extracted antigen by a distinct pathway using small peripheral clusters. Both naive and GC B cell synapses required proximal BCR signaling, but GC cells signaled less through the protein kinase C-beta-NF-kappa B pathway and produced stronger tugging forces on the BCR, thereby more stringently regulating antigen binding. Consequently, GC B cells extracted antigen with better affinity discrimination than naive B cells, suggesting that specialized biomechanical patterns in B cell synapses regulate T cell-dependent selection of high-affinity B cells in GCs.
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