Alitheen N, McClure S, McCullagh P
Developmental Physiology Group, John Curtin School of Medical Research, The Australian National University, Canberra, Australia.
Eur J Immunol. 2001 Sep;31(9):2558-65. doi: 10.1002/1521-4141(200109)31:9<2558::aid-immu2558>3.0.co;2-b.
The B lymphocyte-epithelial cell interactions that define the microenvironment of the ileal Peyer's patch, the primary B lymphocyte organ of the fetal lamb, have been replicated in tissue culture. Mixed suspensions of ileal epithelial cells, lymphocytes and fibroblasts from fetuses of 63-103 days of gestation organized into macroscopically visible agglomerates within 72 h. These agglomerates contained translucent spherical cavities and were enclosed within a marginal cell layer and surrounded by an expanding corona of emigrating cells. The lining of the cavities and the marginal layer consisted of well-differentiated, polarized columnar ileal epithelial cells. One population of B lymphocytes in the initial mixed suspension differentiated into two discrete populations reproducing the characteristics of intact fetal ileal Peyer's patches. B cells apposed to follicle-associated epithelium (FAE) within agglomerates underwent apoptosis. The other population of emigrant B cells proliferated and expressed the BAQ44A differentiation marker. Differentiation of ileal epithelial cells into FAE, typical of Peyer's patches, was markedly accelerated. The mutually inductive influences of intestinal epithelial cells and B lymphocytes in these agglomerates replicate normal mid-gestational fetal development of the mucosal immune system and afford new opportunities for its further investigation.
定义胎羊主要B淋巴细胞器官——回肠派尔集合淋巴结微环境的B淋巴细胞与上皮细胞的相互作用已在组织培养中得以重现。来自妊娠63 - 103天胎儿的回肠上皮细胞、淋巴细胞和成纤维细胞的混合悬液在72小时内组织形成肉眼可见的团聚物。这些团聚物含有半透明的球形腔,被边缘细胞层包围,并被正在迁移的细胞形成的不断扩大的光晕环绕。腔的内衬和边缘层由高度分化的、极化的柱状回肠上皮细胞组成。初始混合悬液中的一群B淋巴细胞分化为两个离散的群体,重现了完整胎儿回肠派尔集合淋巴结的特征。聚集物中与滤泡相关上皮(FAE)相邻的B细胞发生凋亡。另一群迁移的B细胞增殖并表达BAQ44A分化标志物。回肠上皮细胞向派尔集合淋巴结典型的FAE分化明显加速。这些团聚物中肠上皮细胞和B淋巴细胞的相互诱导作用重现了妊娠中期胎儿黏膜免疫系统的正常发育,并为其进一步研究提供了新的机会。