Badr Gamal, Borhis Gwenoline, Lefevre Eric A, Chaoul Nada, Deshayes Frederique, Dessirier Valérie, Lapree Genevieve, Tsapis Andreas, Richard Yolande
Service of Immuno-Virology, Commissariat à l'Energie Atomique, Departement des Sciences du Vivant, Institut des maladies émergentes et therapies innovantes, Unité Mixte de Recherche-E1, Université Paris-Sud, Orsay, France.
Blood. 2008 Mar 1;111(5):2744-54. doi: 10.1182/blood-2007-03-081232. Epub 2008 Jan 2.
B-cell-activating factor of the TNF family, (BAFF), and a proliferation-inducing ligand (APRIL) regulate B-lymphocyte survival and activation. We report that BAFF, but not APRIL, increased the chemotactic response of primary human B cells to CCL21, CXCL12, and CXCL13. The BAFF-induced increase in B-cell chemotaxis was totally abolished by blockade of BAFF-R and was strongly dependent on the activation of PI3K/AKT, NF-kappaB, and p38MAPK pathways. BAFF had similar effects on the chemotaxis of naive and memory B cells in response to CCL21 but increased more strongly that of memory B cells to CXCL13 than that of naive B cells. Our findings indicate a previously unreported role for the BAFF/BAFF-R pair in mature B-cell chemotaxis. The synergy between CXCL13 and BAFF produced by stromal cells and follicular dendritic cells may have important implications for B-cell homeostasis, the development of normal B-cell areas, and for the formation of germinal center-like follicles that may be observed in various autoimmune diseases.
肿瘤坏死因子家族的B细胞激活因子（BAFF）和增殖诱导配体（APRIL）调节B淋巴细胞的存活和激活。我们报告称，BAFF而非APRIL增加了原代人B细胞对CCL21、CXCL12和CXCL13的趋化反应。阻断BAFF-R可完全消除BAFF诱导的B细胞趋化性增加，且其强烈依赖于PI3K/AKT、NF-κB和p38MAPK途径的激活。BAFF对幼稚B细胞和记忆B细胞响应CCL21的趋化性有类似影响，但对记忆B细胞响应CXCL13的趋化性的增强作用比对幼稚B细胞更强。我们的研究结果表明，BAFF/BAFF-R对在成熟B细胞趋化性中具有此前未报道的作用。基质细胞和滤泡树突状细胞产生的CXCL13与BAFF之间的协同作用可能对B细胞稳态、正常B细胞区域的发育以及在各种自身免疫性疾病中可能观察到的生发中心样滤泡的形成具有重要意义。
