B Cell Dynamics Group, Department of Immunology and Oncology, Centro Nacional de Biotecnología/Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Blood. 2011 Aug 11;118(6):1560-9. doi: 10.1182/blood-2011-01-332106. Epub 2011 Jun 9.
Continuous migration of B cells at the follicle contrasts with their stable arrest after encounter with antigen. Two main ligand/receptor pairs are involved in these cell behaviors: the chemokine CXCL13/chemokine receptor CXCR5 and antigen/BCR. Little is known regarding the interplay between CXCR5 and BCR signaling in the modulation of B-cell dynamics and its effect on B-cell activation. We used a 2-dimensional model to study B-cell migration and antigen recognition in real time, and found that BCR signaling strength alters CXCL13-mediated migration, leading to a heterogeneous B-cell behavior pattern. In addition, we demonstrate that CXCL13/CXCR5 signaling does not impair BCR-triggered immune synapse formation and that CXCR5 is excluded from the central antigen cluster. CXCL13/CXCR5 signaling enhances BCR-mediated B-cell activation in at least 2 ways: (1) it assists antigen gathering at the synapse by promoting membrane ruffling and lymphocyte function-associated antigen 1 (LFA-1)-supported adhesion, and (2) it allows BCR signaling integration in motile B cells through establishment of LFA-1-supported migratory junctions. Both processes require functional actin cytoskeleton and non-muscle myosin II motor protein. Therefore, the CXCL13/CXCR5 signaling effect on shaping B-cell dynamics is an effective mechanism that enhances antigen encounter and BCR-triggered B-cell activation.
B 细胞在滤泡中的持续迁移与它们与抗原相遇后的稳定停滞形成对比。有两个主要的配体/受体对参与了这些细胞行为：趋化因子 CXCL13/趋化因子受体 CXCR5 和抗原/BCR。关于 CXCR5 和 BCR 信号在调节 B 细胞动力学及其对 B 细胞激活的影响方面的相互作用知之甚少。我们使用二维模型实时研究 B 细胞迁移和抗原识别，发现 BCR 信号强度改变了 CXCL13 介导的迁移，导致 B 细胞行为模式的异质性。此外，我们证明 CXCL13/CXCR5 信号不会损害 BCR 触发的免疫突触形成，并且 CXCR5 被排除在中央抗原簇之外。CXCL13/CXCR5 信号至少通过两种方式增强 BCR 介导的 B 细胞激活：(1) 通过促进细胞膜皱襞和淋巴细胞功能相关抗原 1（LFA-1）支持的黏附，促进抗原在突触处聚集，以及 (2) 通过建立 LFA-1 支持的迁移连接，允许 BCR 信号在运动中的 B 细胞中进行整合。这两个过程都需要功能性肌动蛋白细胞骨架和非肌肉肌球蛋白 II 运动蛋白。因此，CXCL13/CXCR5 信号对塑造 B 细胞动力学的影响是一种增强抗原相遇和 BCR 触发 B 细胞激活的有效机制。
