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CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics
Blood ( IF 21.0 ) Pub Date : 2011-08-11 , DOI: 10.1182/blood-2011-01-332106
Julia Sáez de Guinoa 1 , Laura Barrio , Mario Mellado , Yolanda R Carrasco
Affiliation  

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.

中文翻译:

CXCL13/CXCR5 信号通过塑造细胞动力学增强 BCR 触发的 B 细胞活化

B 细胞在毛囊中的连续迁移与它们在遇到抗原后的稳定停滞形成对比。这些细胞行为涉及两个主要的配体/受体对:趋化因子 CXCL13/趋化因子受体 CXCR5 和抗原/BCR。关于 CXCR5 和 BCR 信号在 B 细胞动力学调节中的相互作用及其对 B 细胞活化的影响知之甚少。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,导致了异质性 B 细胞行为模式。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 信号通过至少两种方式增强 BCR 介导的 B 细胞活化:(1) 它通过促进膜皱褶和淋巴细胞功能相关抗原 1 (LFA-1) 支持的粘附来协助抗原在突触处聚集,以及( 2) 通过建立 LFA-1 支持的迁移连接,它允许 BCR 信号整合到活动 B 细胞中。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增强抗原遭遇和 BCR 触发的 B 细胞活化的有效机制。(2) 通过建立 LFA-1 支持的迁移连接,它允许 BCR 信号整合到活动 B 细胞中。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增强抗原遭遇和 BCR 触发的 B 细胞活化的有效机制。(2) 通过建立 LFA-1 支持的迁移连接,它允许 BCR 信号整合到活动 B 细胞中。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增强抗原遭遇和 BCR 触发的 B 细胞活化的有效机制。
更新日期:2011-08-11
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