In vitro and in vivo activation induces BAFF and APRIL expression in B cells
In vitro and in vivo activation induces BAFF and APRIL expression in B cells
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DOI：
10.4049/jimmunol.179.9.5947
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发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Berek, Claudia
中科院分区：
文献类型：
--
作者：
Chu, Van Trung;Enghard, Philipp;Berek, Claudia
B细胞激活因子(BA.FF)和增殖诱导配体(APRIL)在外周B细胞的存活、成熟和分化中起关键作用。BAFF和APRIL由多种细胞类型产生，如巨噬细胞/单核细胞和树突状细胞。我们的分析表明，BAFF mRNA也在BALB/c小鼠的骨髓、脾和腹膜腔分离的所有B细胞亚群中表达。APRIL的表达仅限于骨髓和腹膜B1亚群中B细胞发育的早期阶段。用脂多糖或CpG-寡核苷酸刺激B2和B1细胞，诱导MyD88依赖的浆细胞分化和BAFF和APRIL在细胞内的表达。此外，B细胞的激活上调了BAFF的膜表达。拮抗剂跨膜激活剂和钙调节剂配体相互作用Ig抑制B细胞的体外激活，表明BAFF和/或APRIL被释放到培养上清液中。这表明B细胞的生存、增殖和分化是由自分泌途径支持的。T依赖的Ag诱导生发中心B细胞表达BAFF体内激活B细胞。在(NZB X NZW)F小鼠中，已建立的自身免疫性疾病小鼠的边缘带、生发中心B细胞以及脾浆细胞表达高水平的BAFF。在(NZB X NZW)F-1小鼠中，B细胞的持续激活从而过度表达BAFF和APRIL可能参与了自身免疫性疾病的发生。
B cell-activating factor (BA.FF) and a proliferation-inducing ligand (APRIL) play key roles in peripheral B cell survival, maturation, and differentiation. BAFF and APRIL are produced by a variety of cell types such as macrophages/monocytes and dendritic cells. Our analysis shows that BAFF mRNA is also expressed in all B cell subsets isolated from bone marrow, spleen, and peritoneal cavity of BALB/c mice. APRIL expression is restricted to early stages of B cell development in the bone marrow and the peritoneal B1 subset. Stimulation of B2 and B1 cells with LPS or CpG-oligodeoxynucleotides induced MyD88-dependent plasma cell differentiation and intracellular expression of BAFF and APRIL. Furthermore, activation of B cells up-regulated membrane expression of BAFF. The finding that in vitro activation of B cells is inhibited by the antagonist transmembrane activator and calcium modulator ligand interactor Ig, indicates that BAFF and/or APRIL are released into the culture supernatants. It shows that B cell survival, proliferation, and differentiation are supported by an autocrine pathway. In vivo activation of B cells with a T-dependent Ag- induced BAFF expression in germinal center B cells. In (NZB X NZW)F, mice with established autoimmune disease, marginal zone, germinal center B cells, as well as splenic plasma cells expressed high levels of BAFF. In (NZB X NZW)F-1 mice, the continuous activation of B cells and thus overexpression of BAFF and APRIL may contribute to the development of autoimmune disease.