Myrdal S E, Snoddy S, Ashkar S, Nixon D W, Binkley F
J Immunol. 1983 Aug;131(2):869-76.
IgA secretion by the lactating mammary gland culminates a complex sequence of biologic events both within the gland and at distant sites. Because of the many extraglandular influences, it is difficult to investigate IgA secretion at the tissue and cellular levels in the intact animal. In this study, with the use of immunohistofluorescence, we have observed elaboration of IgA by primary monolayer cultures of mammary cells from the glands of mid-pregnant mice and from mammary tumors. In cultures of normal cells, IgA appeared first in vesicular structures on the upper surfaces of the monolayers. Vesicular IgA was maximal at day 5 in culture, and at that time, was observed only over mounds (domelike structures) that were covered with fibrillar fibronectin (FN), and eventually developed a subpopulation of fusiform cells. It appears that the IgA observed was secreted in vitro, that normal mammary epithelial cells must form multicellular FN-bearing structures to secrete IgA in culture, and that by mid-pregnancy the murine mammary gland contains all of the lymphoid cells required for IgA secretion. In contrast, primary cultures of mammary tumors displayed minimal amounts of IgA and FN. The small amount of cell-associated IgA that was detected on tumor cultures was not localized to any multicellular structures nor was it associated with FN, but instead appeared as minute, punctate accumulations on individual cells scattered across the epithelioid areas. This finding is consistent with the loss of specialized functions and the increased autonomy typical of malignant cells. The study in cultured cells of a function as specialized as IgA secretion should permit greater understanding of both the process itself and the despecializations that accompany malignancies of secretory epithelia.
哺乳期乳腺分泌的IgA是腺体内部及远处一系列复杂生物学事件的 culminates。由于存在许多腺体外影响因素,在完整动物体内研究组织和细胞水平的IgA分泌较为困难。在本研究中,我们利用免疫组织荧光技术,观察了来自妊娠中期小鼠腺体和乳腺肿瘤的乳腺细胞原代单层培养物中IgA的形成。在正常细胞培养物中,IgA首先出现在单层细胞上表面的囊泡结构中。囊泡状IgA在培养第5天时达到最大值,此时仅在覆盖有纤维状纤连蛋白(FN)的隆起(穹顶状结构)上观察到,最终形成梭形细胞亚群。似乎观察到的IgA是在体外分泌的,正常乳腺上皮细胞在培养中必须形成含FN的多细胞结构才能分泌IgA,并且到妊娠中期时,小鼠乳腺已含有IgA分泌所需的所有淋巴细胞。相比之下,乳腺肿瘤原代培养物中显示出极少量的IgA和FN。在肿瘤培养物中检测到的少量细胞相关IgA既未定位到任何多细胞结构,也未与FN相关联,而是表现为散布在上皮样区域单个细胞上的微小点状聚集物。这一发现与恶性细胞典型的特殊功能丧失和自主性增加相一致。对像IgA分泌这样特殊功能的培养细胞进行研究,应该能够更深入地了解这一过程本身以及分泌上皮恶性肿瘤伴随的去分化现象。