All leukocytes can get entrance into the draining lymph nodes via the afferent lymphatics but only lymphoid cells can leave the nodes. The molecular mechanisms behind this phenomenon have remained unknown. We employed genome wide microarray analyses of the subcapsular sinus and lymphatic sinus (LS) endothelial cells and found Robo4 to be selectively expressed on LS lymphatics. Further analyses showed high Robo4 expression in lymphatic vessels of Peyer’s patches, which only have efferent lymphatic vessels. In functional assays, Robo4-deficient animals showed accumulation of naïve B cells (CD19⁺/CD62L^hi/CD44^lo) in Peyer’s patches, whereas no difference was seen within other lymphocyte subtypes. Short-term lymphocyte homing via high endothelial venules to peripheral and mesenteric lymph nodes and Peyer’s patches was also slightly impaired in Robo4 knockout animals. These results show for the first time, selective expression of Robo4 in the efferent arm of the lymphatics and its role in controlling the turnover of a subset of B lymphocytes from Peyer’s patches.

所有白细胞都可以通过传入淋巴管进入引流淋巴结，但只有淋巴样细胞可以离开淋巴结。这种现象背后的分子机制仍然未知。我们对囊下窦和淋巴窦 (LS) 内皮细胞进行了全基因组微阵列分析，发现 Robo4 在 LS 淋巴管上有选择性地表达。进一步分析显示，Peyer 淋巴结的淋巴管中 Robo4 高表达，只有传出淋巴管。在功能测定中，Robo4 缺陷动物表现出幼稚 B 细胞的积累（CD19 ⁺ /CD62L ^hi /CD44 ^lo) 在 Peyer 的斑块中，而在其他淋巴细胞亚型中没有发现差异。通过高内皮微静脉到外周和肠系膜淋巴结和淋巴集结的短期淋巴细胞归巢在 Robo4 基因敲除动物中也略有受损。这些结果首次显示了 Robo4 在淋巴管传出臂中的选择性表达及其在控制淋巴集结 B 淋巴细胞亚群更新中的作用。