Kranich Jan, Krautler Nike Julia, Heinen Ernst, Polymenidou Magdalini, Bridel Claire, Schildknecht Anita, Huber Christoph, Kosco-Vilbois Marie H, Zinkernagel Rolf, Miele Gino, Aguzzi Adriano
Institute of Neuropathology, University Hospital of Zurich, 8091 Zurich, Switzerland.
J Exp Med. 2008 Jun 9;205(6):1293-302. doi: 10.1084/jem.20071019. Epub 2008 May 19.
The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMphis). Impairment of this process can contribute to autoimmunity. We show that Mfge8 is identical to the mouse follicular dendritic cell (FDC) marker FDC-M1. In bone-marrow chimeras between wild-type and Mfge8(-/-) mice, all splenic Mfge8 was derived from FDCs rather than TBMphis. However, Mfge8(-/-) TBMphis acquired and displayed Mfge8 only when embedded in Mfge8(+/+) stroma, or when situated in lymph nodes draining exogenous recombinant Mfge8. These findings indicate a licensing role for FDCs in TBMphi-mediated removal of excess B cells. Lymphotoxin-deficient mice lacked FDCs and splenic Mfge8, and suffer from autoimmunity similar to Mfge8(-/-) mice. Hence, FDCs facilitate TBMphi-mediated corpse removal, and their malfunction may be involved in autoimmunity.
分泌型磷脂酰丝氨酸结合蛋白乳脂肪球表皮生长因子8（Mfge8）介导凋亡生发中心B细胞被吞噬体巨噬细胞（TBMphis）吞噬。这一过程受损可能导致自身免疫。我们发现Mfge8与小鼠滤泡树突状细胞（FDC）标志物FDC-M1相同。在野生型和Mfge8（-/-）小鼠之间的骨髓嵌合体中，所有脾脏Mfge8均来源于FDC而非TBMphis。然而，Mfge8（-/-）TBMphis仅在嵌入Mfge8（+/+）基质中，或位于引流外源性重组Mfge8的淋巴结中时，才获得并展示Mfge8。这些发现表明FDC在TBMphi介导的清除多余B细胞过程中具有许可作用。淋巴毒素缺陷小鼠缺乏FDC和脾脏Mfge8，并患有与Mfge8（-/-）小鼠相似的自身免疫。因此，FDC促进TBMphi介导的尸体清除，其功能障碍可能与自身免疫有关。
