Burkly L, Hession C, Ogata L, Reilly C, Marconi L A, Olson D, Tizard R, Cate R, Lo D
Biogen Inc., Cambridge, Massachusetts 02142.
Nature. 1995 Feb 9;373(6514):531-6. doi: 10.1038/373531a0.
Dendritic cells (DC) derived from bone marrow are critical in the function of the immune system, for they are the primary antigen-presenting cells in the activation of T-lymphocyte response. Their differentiation from precursor cells has not been defined at a molecular level, but recent studies have shown an association between expression of the relB subunit of the NF-kappa B complex and the presence of DC in specific regions of normal unstimulated lymphoid tissues. Here we show that relB expression also correlates with differentiation of DC in autoimmune infiltrates in situ, and that a mutation disrupting the relB gene results in mice with impaired antigen-presenting cell function, and a syndrome of excess production of granulocytes and macrophages. Thymic UEA-1+ medullary epithelial cells from normal mice show striking similarities to DC and, interestingly, these cells are also absent in relB mutant mice. Taken together, these results suggest that relB is critical in the coordinated activation of genes necessary for the differentiation of two unrelated but phenotypically similar cells (DC and thymic UEA-1+ medullary epithelial cells) and is therefore a candidate for a gene determining lineage commitment in the immune system.
源自骨髓的树突状细胞（DC）在免疫系统功能中至关重要，因为它们是激活T淋巴细胞反应的主要抗原呈递细胞。它们从祖细胞的分化在分子水平上尚未明确，但最近的研究表明，NF-κB复合物的relB亚基的表达与正常未受刺激的淋巴组织特定区域中DC的存在之间存在关联。在这里，我们表明relB表达也与原位自身免疫浸润中DC的分化相关，并且破坏relB基因的突变导致小鼠抗原呈递细胞功能受损，以及粒细胞和巨噬细胞过度产生的综合征。正常小鼠的胸腺UEA-1 +髓质上皮细胞与DC有显著相似性，有趣的是，这些细胞在relB突变小鼠中也不存在。综上所述，这些结果表明relB对于两种不相关但表型相似的细胞（DC和胸腺UEA-1 +髓质上皮细胞）分化所需基因的协同激活至关重要，因此是决定免疫系统谱系定向的基因候选者。
