Nowosad Carla R, Spillane Katelyn M, Tolar Pavel
Laboratory of Activation of Immune Receptors, Francis Crick Institute, Mill Hill Laboratory, London, UK.
Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London, UK.
Nat Immunol. 2016 Jul;17(7):870-7. doi: 10.1038/ni.3458. Epub 2016 May 16.
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-β-NF-κB 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.
B细胞活化受免疫突触中B细胞抗原受体（BCR）信号传导和抗原内化的调节。通过对B细胞亚群进行大规模成像，我们发现，与幼稚B细胞和记忆B细胞在抗原内化前将抗原聚集到突触中心不同，生发中心（GC）B细胞通过使用外周小簇的独特途径提取抗原。幼稚B细胞和GC B细胞突触都需要近端BCR信号传导，但GC细胞通过蛋白激酶C-β-NF-κB途径发出的信号较少，并且对BCR产生更强的拉力，从而更严格地调节抗原结合。因此，GC B细胞比幼稚B细胞以更好的亲和力辨别提取抗原，这表明B细胞突触中的特殊生物力学模式调节GC中高亲和力B细胞的T细胞依赖性选择。
