BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells

BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells
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DOI:
10.1182/blood-2007-03-081232
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发表时间:
2008-03-01
期刊:
影响因子:
20.3
通讯作者:
Richard, Yolande
Richard, Yolande
中科院分区:
医学1区
文献类型:
--
作者:
Badr, Gamal;Borhis, Gwenoline;Richard, Yolande

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TNF家族的B细胞活化因子(BAFF)和增殖诱导配体(APRIL)调节B淋巴细胞的存活和活化。我们报道BAFF而非APRIL增加了原代人B细胞对CCL 21、CXCL 12和CXCL 13的趋化反应。BAFF-R的阻断完全消除了BAFF诱导的B细胞趋化性的增加,并且强烈依赖于PI 3 K/AKT、NF-κ B和p38 MAPK通路的激活。BAFF对幼稚和记忆B细胞对CCL 21的趋化作用相似,但对记忆B细胞对CXCL 13的趋化作用比幼稚B细胞更强。我们的研究结果表明,以前未报道的作用BAFF/BAFF-R对成熟的B细胞趋化性。由基质细胞和滤泡树突状细胞产生的CXCL 13和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可能在各种自身免疫性疾病中观察到的生发中心样滤泡的形成具有重要意义。
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-kappa B, 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.