Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice
Generation of splenic follicular structure and B cell movement in tumor necrosis factor-deficient mice
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DOI：
10.1084/jem.188.8.1503
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发表时间：
1998-10-19
影响因子：
15.3
通讯作者：
Basten, A
中科院分区：
文献类型：
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作者：
Cook, MC;Körner, H;Basten, A
次级淋巴组织器官发生需要肿瘤坏死因子（TNF）和α-光敏素（LT α）。通过比较TNF-/-和TNF/LT α（-/-）小鼠中新产生的幼稚再循环和抗原刺激的B细胞的位置，研究了TNF在B细胞定位和滤泡结构形成中的作用。通过从野生型和TNF-/-小鼠中产生辐射骨髓嵌合体，显示正常脾B细胞滤泡的形成依赖于造血来源的辐射敏感细胞的TNF产生。成熟B细胞在野生型和基因敲除小鼠之间的相互过继转移表明，再循环幼稚B细胞的正常滤泡向性独立于来自受体脾脏的TNF而发生。此外，体内施用可溶性TNF受体-IgG融合蛋白未能阻止B细胞定位于卵泡或生发中心反应。当抗原刺激的B细胞被转移到TNF-/-受体中时，观察到正常的T区嗜性，但不转移到TNF/LT α（-/-）受体中。该结果似乎解释了在完整TNF/LT α（-/-）小鼠中观察到的同种型转换缺陷，因为TNF/LT α（-/-）B细胞在体外刺激时正常转换同种型。因此，TNF是创造B细胞运动和功能的容许环境所必需的，但其本身并不负责这些过程。
Secondary lymphoid tissue organogenesis requires tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha). The role of TNF in B cell positioning and formation of follicular structure was studied by comparing the location of newly produced naive recirculating and antigen-stimulated B cells in TNF-/- and TNF/LT alpha(-/-) mice. By creating radiation bone marrow chimeras from wild-type and TNF-/- mice, formation of normal splenic B cell follicles was shown to depend on TNF production by radiation-sensitive cells of hemopoietic origin. Reciprocal adoptive transfers of mature B cells between wild-type and knockout mice indicated that normal follicular tropism of recirculating naive B cells occurs independently of TNF derived from the recipient spleen. Moreover, soluble TNF receptor-IgG fusion protein administered in vivo failed to prevent B cell localization to the follicle or the germinal center reaction. Normal T zone tropism was observed when antigen-stimulated B cells were transferred into TNF-/- recipients, but not into TNF/LT alpha(-/-) recipients. This result appeared to account for the defect in isotype switching observed in intact TNF/LT alpha(-/-) mice because TNF/LT alpha(-/-) B cells, when stimulated in vitro, switched isotypes normally. Thus, TNF is necessary for creating the permissive environment for B cell movement and function, but is not itself responsible for these processes.