Splenic T zone development is B cell dependent.
Splenic T zone development is B cell dependent.
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DOI：
10.1084/jem.194.11.1649
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发表时间：
2001-12-03
影响因子：
15.3
通讯作者：
Cyster, J G
中科院分区：
文献类型：
--
作者：
Ngo, V N;Cornall, R J;Cyster, J G
调节脾脏生长和形成的因素还不清楚。我们在这里证明，脾从B细胞缺陷小鼠的T区趋化因子，CCL 21的表达减少了10倍，T细胞和树突状细胞（DC）的数量减少了3倍，和减少表达的T区基质标记，gp38。使用细胞转移和受体阻断的方法，我们提供的证据表明，B细胞在出生后早期的脾脏T区的发展中起着至关重要的作用。该过程涉及B细胞表达CCL 21和gp38表达所需的细胞因子光毒素（LT）α1β2。将B细胞特异性LTα转基因导入LTα缺陷背景，恢复了脾脏CCL 21和gp38表达、DC数量和T区大小。这项工作还表明，B细胞在T区发育中的作用与B细胞对脾脏T细胞数量的影响不同，后者不需要LTα1β2。因此，B细胞通过提供：（a）促进T细胞积累的信号，和（B）促进基质细胞发育和DC积累的信号（包括LTα1β2）来影响脾T区发育。这些参数的缺陷可能导致与小鼠和人类B细胞缺乏相关的免疫缺陷。
The factors regulating growth and patterning of the spleen are poorly defined. We demonstrate here that spleens from B cell–deficient mice have 10-fold reduced expression of the T zone chemokine, CCL21, a threefold reduction in T cell and dendritic cell (DC) numbers, and reduced expression of the T zone stromal marker, gp38. Using cell transfer and receptor blocking approaches, we provide evidence that B cells play a critical role in the early postnatal development of the splenic T zone. This process involves B cell expression of lymphotoxin (LT)α1β2, a cytokine that is required for expression of CCL21 and gp38. Introduction of a B cell specific LTα transgene on to the LTα-deficient background restored splenic CCL21 and gp38 expression, DC numbers, and T zone size. This work also demonstrates that the role of B cells in T zone development is distinct from the effect of B cells on splenic T cell numbers, which does not require LTα1β2. Therefore, B cells influence spleen T zone development by providing: (a) signals that promote T cell accumulation, and: (b) signals, including LTα1β2, that promote stromal cell development and DC accumulation. Defects in these parameters may contribute to the immune defects associated with B cell deficiency in mice and humans.