Montrasio F, Cozzio A, Flechsig E, Rossi D, Klein M A, Rülicke T, Raeber A J, Vosshenrich C A, Proft J, Aguzzi A, Weissmann C
Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4034-7. doi: 10.1073/pnas.051609398. Epub 2001 Mar 13.
Prion replication in spleen and neuroinvasion after i.p. inoculation of mice is impaired in forms of immunodeficiency where mature B lymphocytes are lacking. In spleens of wild-type mice, infectivity is associated with B and T lymphocytes and stroma but not with circulating lymphocytes. We generated transgenic prion protein knockout mice overexpressing prion protein in B lymphocytes and found that they failed to accumulate prions in spleen after i.p. inoculation. We conclude that splenic B lymphocytes are not prion-replication competent and that they acquire prions from other cells, most likely follicular dendritic cells with which they closely associate and whose maturation depends on them.
在缺乏成熟B淋巴细胞的免疫缺陷形式下，小鼠腹腔接种后朊病毒在脾脏中的复制及神经侵袭会受到损害。在野生型小鼠的脾脏中，感染性与B淋巴细胞、T淋巴细胞及基质相关，而与循环淋巴细胞无关。我们构建了在B淋巴细胞中过表达朊病毒蛋白的转基因朊病毒蛋白敲除小鼠，发现它们腹腔接种后脾脏中未能积累朊病毒。我们得出结论，脾脏B淋巴细胞不具备朊病毒复制能力，它们从其他细胞获取朊病毒，最有可能是与其紧密关联且其成熟依赖于它们的滤泡树突状细胞。
