目的：探讨单独或共同表达视黄酸早期转录因子1ε（retinoic acid early transcript 1ε，RAE1ε）和膜型IL-15的B淋巴细胞BaF3对小鼠产生IFN的杀伤性DC（IFN producing killer DC，IKDC）功能分子表达的影响。方法：以小鼠原B淋巴细胞株BaF3为基础，分别构建表达膜型IL-15的BaF3-mb15细胞和表达RAE1ε的BaF3-RAE细胞及同时表达膜型IL-15和RAE1ε的BaF3-mb15-RAE细胞。通过体外细胞因子诱导产生骨髓来源的小鼠成熟DC，将丝裂霉素灭活后的3株BaF3工程细胞株作为刺激细胞，分别与DC共培养，流式细胞术检测其对DC中CD11clowB220+NK1.1+IKDC比例和DC表面CD40、CD80表达的影响。流式细胞术分选DC中的IKDC，将丝裂霉素灭活后的3株BaF3工程细胞株与其共培养24 h，流式细胞术检测共培养对IKDC表面CD40、CD80、CD86、NKG2D、MHCⅡ类分子、CD107a和FasL表达的影响。结果：成功获得骨髓来源的小鼠成熟DC。与BaF3-mb15细胞和BaF3-RAE细胞相比，BaF3-mb15-RAE细胞刺激显著提高DC中IKDC比例\[（50.0±5.6）% vs （30.3±8.2）%、（36.0±4.6）%，均 P <0.05\]，并且有效刺激IKDC表面CD40(180.1±28.2 vs 44.7±7.8、36.0±3.1, P <001)和FasL（ P <0.05）表达上调；与BaF3细胞和BaF3-mb15细胞相比，BaF3-mb15-RAE细胞有效刺激IKDC表面CD80（ P <0.05）表达上调，而3株BaF3工程细胞刺激均不影响DC表面CD40、CD80的表达（ P >0.05）；同时，3株BaF3工程细胞对IKDC表面CD86、MHC Ⅱ类分子、NKG2D和CD107a的表达也没有显著影响（ P >0.05）。结论：RAE-1ε和膜型IL-15协同作用可促进IKDC增殖并诱导其高表达CD40和FasL。

Objective: To study the effects of murine bone marrow-derived pro-B (BaF3) cells overexpressing membrane-bound form of IL-15 (mbIL-15) and retinoic acid early transcript 1ε (RAE1ε), either each alone or two in combination, on the expression of functional molecules in murine interferon producing killer dendritic cells (IKDCs) in vitro . Methods: Clones of BaF3 cells overexpressing mbIL-15 , RAE1ε or both mbIL-15 and RAE1ε were established and inactivated by mitomycin. Mouse bone marrow mononuclear cells were isolated and induced into mature DCs by GM-CSF and IL-4. Mature DCs were co-cultured with the three mitomycin inactivated-BaF3 derivatives respectively. At 24 and 72 hours after co-culture, the percentage of CD11clow B220+NK1.1+ IKDCs and levels of CD40 and CD80 in DCs and levels of CD40, CD80, CD86, NKG2D, MHC class Ⅱ molecule, CD107a and FasL in IKDCs were determined by flow cytometry. Results: BaF3 cells overexpressing both mbIL-15 and RAE were more effective than BaF3 cells overexpressing mbIL-15 or RAE alone to stimulate the DC to IKDC conversion (\[50.0±5.6\]% vs \[30.3±8.2\]%, \[36.0±4.6\]%, P <0.05). IKDCs co-cultured with BaF3 cells overexpressing mbIL-15 and RAE had higher levels of CD40 (180.1±282 vs 44.7±7.8, 36.0±3.1, P <0.01) and FasL ( P <0.05) as compared to IKDCs co-cultured with mbIL-15- or RAE-overexpressing BaF3 cells. IKDCs co-cultured with BaF3 cells overexpressing mbIL-15 and RAE had higher levels of CD80 ( P <0.05) as compared to IKDCs co-cultured with BaF3 cells or mbIL-15-overexpressing BaF3 cells. In contrast, co-culture with BaF3 derivatives showed no effects either on CD40 and CD80 expression in DCs ( P >0.05)or on CD86, MHC class Ⅱ molecule, NKG2D and CD107a expression in IKDCs. Conclusion: IL-15 combined with RAE1ε may promote the proliferation and CD40 and FasL expression in IKDCs.

国家自然科学基金资助项目（No.81001308，No. 81373130，No. 81273214）；江苏省自然科学基金资助项目（No. BK2010315）；江苏省大学生创新创业训练计划项目；扬州大学“新世纪人才工程”资助。