Fibrinogen is localized on dark zone follicular dendritic cells in vivo and enhances the proliferation and survival of a centroblastic cell line in vitro
Fibrinogen is localized on dark zone follicular dendritic cells in vivo and enhances the proliferation and survival of a centroblastic cell line in vitro
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DOI：
10.1189/jlb.0107050
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发表时间：
2007-09-01
影响因子：
5.5
通讯作者：
Charleston, Bryan
中科院分区：
文献类型：
--
作者：
Lefevre, Eric A.;Hein, Wayne R.;Charleston, Bryan
次级淋巴器官的生发中心（GC）中的滤泡树突状细胞（FDC）增加抗原刺激的B细胞的存活和增殖，并且对于抗体应答的亲和力成熟和B细胞免疫记忆的维持是关键的。暗区（DZ）和亮区（LZ）构成GC的不同区域，含有不同亚型的FDC，如通过其形态学和表型鉴定的。到目前为止，大多数可用的FDC特异性试剂识别LZ FDC，并且没有特异性识别DZ FDC的试剂。在这里，我们报告了一种新的单克隆抗体，D46，染色FDC特异性在DZ的牛和绵羊GC的次级卵泡内。我们确定其配体为牛纤维蛋白原，并使用市售的抗人纤维蛋白原抗体，表明这种炎症蛋白也存在于腭扁桃体内人GC的DZ FDC上。在体外，外源性纤维蛋白原的加入刺激BCR刺激的L3055细胞的增殖和存活，其构成中心母细胞的克隆群体并保留正常GC B细胞的重要特征。总之，我们的研究结果表明，纤维蛋白原定位在DZ FDC可以支持广泛的增殖和生存的GC B细胞内的DZ在体内。
Follicular dendritic cells (FDC) in the germinal centers (GC) of secondary lymphoid organs increase the survival and proliferation of antigen-stimulated B cells and are pivotal for the affinity maturation of an antibody response and for maintenance of B cell immunological memory. The dark zone (DZ) and the light zone (LZ) constitute distinct areas of the GC containing different subtypes of FDC as identified by their morphology and phenotype. Until now, most available FDC-specific reagents identify LZ FDC, and there are no reagents recognizing DZ FDC specifically. Here, we report a new mAb, D46, which stains FDC specifically in the DZ of bovine and ovine GC within the secondary follicles. We identify its ligand as bovine fibrinogen, and using commercially available antihuman fibrinogen antibodies, show that this inflammatory protein is also present on DZ FDC of human GC within palatine tonsils. In vitro, the addition of exogenous fibrinogen stimulates the proliferation and survival of BCR-stimulated L3055 cells, which constitute a clonal population of centroblastic cells and retain important features of normal GC B cells. Together, our results suggest that fibrinogen localized on DZ FDC could support the extensive proliferation and survival of GC B cells within the DZ in vivo.