Peebles R S, Maliszewski C R, Sato T A, Hanley-Hyde J, Maroulakou I G, Hunziker R, Schneck J P, Green J E
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224.
Oncogene. 1995 Mar 16;10(6):1045-51.
Transgenic mice that carry the HTLV-I Tax gene develop an exocrinopathy with some similarities to Sjoegren's syndrome. Our experiments reveal that these mice have lymphadenopathy and splenomegaly composed primarily of B lymphocytes, as well as abnormal levels of secreted immunoglobulins. To gain insight into whether the lymphadenopathy manifested by these transgenic mice was the result of induction of cytokines by Tax, we utilized cell lines from these mice to study in vitro B-cell responses. Conditioned media (CM) derived from the cell lines caused B-cells to proliferate when a second signal, surface Ig cross-linking, was provided. The CM also caused a marked enhancement of IgM secretion by spleen cells or by purified B-cells treated with supplemental cytokines. The B-cell proliferative response and enhanced IgM secretion have not been attributed to a known cytokine. These results suggest that the CM from the cell lines contain a factor(s) involved in novel pathways of B-cell growth and differentiation that may participate in the pathologic development of autoimmune disease.
携带HTLV-I Tax基因的转基因小鼠会出现一种与干燥综合征有某些相似之处的外分泌腺病。我们的实验表明,这些小鼠患有主要由B淋巴细胞组成的淋巴结病和脾肿大,以及分泌型免疫球蛋白水平异常。为了深入了解这些转基因小鼠表现出的淋巴结病是否是Tax诱导细胞因子的结果,我们利用这些小鼠的细胞系来研究体外B细胞反应。当提供第二个信号(表面Ig交联)时,来自细胞系的条件培养基(CM)会使B细胞增殖。CM还显著增强了脾细胞或用补充细胞因子处理的纯化B细胞的IgM分泌。B细胞增殖反应和增强的IgM分泌尚未归因于已知的细胞因子。这些结果表明,来自细胞系的CM含有参与B细胞生长和分化新途径的一种或多种因子,这些因子可能参与自身免疫性疾病的病理发展。