Role of CD30 in B/T segregation in the spleen

Role of CD30 in B/T segregation in the spleen
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DOI:
10.4049/jimmunol.179.11.7535
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发表时间:
2007-12-01
影响因子:
4.4
通讯作者:
Lane, Peter J. L.
Lane, Peter J. L.
中科院分区:
医学2区
文献类型:
--
作者:
Bekiaris, Vasileios;Withers, David;Lane, Peter J. L.

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在这份报告中,我们确定了一个重要的功能,CD 30信号的有效隔离的B和T淋巴细胞在小鼠脾脏,除了公认的要求,光毒素信号。我们发现,CD 30信号不需要转录或蛋白表达的稳态趋化因子,但CD 30缺陷小鼠显示受损的B/T分离。这种缺陷与T区基质上跨膜粘蛋白型蛋白podoplanin的Ab检测到的缺陷性表达相关,尽管在其他位点的表达是正常的。缺陷性分离不是CD 30缺陷型淋巴细胞固有的,CD 30缺陷型淋巴细胞在转移到RAG缺陷型小鼠后正常分离,并显著上调RAG缺陷型小鼠T区基质上CCL 21和podoplanin的表达。在发育过程中,淋巴组织诱导细胞诱导CD 30配体表达和T区基质诱导podoplanin表达在时间上是相关的,这些细胞的空间关联表明淋巴组织诱导细胞能够提供CD 30信号。最后,我们表明,podoplanin的外观上的T区间质的发展与B/T分离的脾白色髓区。我们的研究表明,稳态趋化因子表达本身不足以进行B/T分离,我们的数据指出了podoplanin或与podoplanin表达基质相关的分子在淋巴细胞的有效分离中的重要作用。
In this report, we identify an important function for CD30 signals in the effective segregation of B and T lymphocytes in the murine spleen, additional to the recognized requirement for lymphotoxin signals. We show that CD30 signals are not required for transcription or protein expression of homeostatic chemokines, but CD30-deficient mice display impaired B/T segregation. This defect correlates with defective expression as detected by Abs of the transmembrane mucin-type protein podoplanin on T zone stroma, although expression at other sites is normal. Defective segregation is not intrinsic to CD30-deficient lymphocytes which segregate normally following transfer into RAG-deficient mice and significantly up-regulate the expression of both CCL21 and podoplanin on T zone stroma of RAG-deficient mice. During development, induction of expression of the CD30 ligand by lymphoid tissue inducer cells and podoplanin by T zone stroma are temporally linked, and the spatial association of these cells suggests that lymphoid tissue inducer cells are capable of providing the CD30 signals. Finally, we show that the appearance of podoplanin on T zone stroma in development is associated with B/T segregation of splenic white pulp areas. Our studies indicate that homeostatic chemokine expression by itself is not sufficient for B/T segregation and our data point to a significant role for podoplanin or molecules associated with podoplanin expressing stroma in the effective segregation of lymphocytes.