Ryffel B, Di Padova F, Schreier M H, Le Hir M, Eugster H P, Quesniaux V F
Institute of Pathology, University of Basel, Switzerland.
J Immunol. 1997 Mar 1;158(5):2126-33.
TNF is implicated in in vitro Ig production, but its role in vivo is not clearly defined. Our previous studies had shown that TNF-LT alpha double-deficient mice have defective IgM and IgG primary Ab responses to the T cell-dependent (TD) Ag SRBC. We now extend these studies to secondary responses and to T cell-independent (TI) B cell responses. Injections of the TD Ag SRBC did not induce germinal center formation in the spleen of TNF-LT alpha-deficient mice. Associated with the morphologic defect, there was a defective IgG Ab response and a secondary hyper-IgM response to the TD Ag in TNF-LT alpha-deficient mice. The response to the TI Ag type 2 DNP-alanyl-glycyl-glycyl-Ficoll was essentially absent in TNF-LT alpha-deficient mice, while that to the TI Ag type 1 TNP-LPS was significantly reduced only for IgG2b isotype. Transplantation of bone marrow cells from wild-type mice into irradiated TNF-LT alpha-deficient mice restored the formation of splenic germinal centers and corrected the IgM and IgG responses to both TD and TI Ags. These data suggest that TNF and/or LT alpha signaling are critically required for germinal center formation and for the IgM and IgG responses to both TD and TI type 2 Ags.
肿瘤坏死因子（TNF）与体外免疫球蛋白（Ig）的产生有关，但其在体内的作用尚未明确界定。我们之前的研究表明，TNF -淋巴毒素α（LTα）双缺陷小鼠对T细胞依赖性（TD）抗原绵羊红细胞（SRBC）的IgM和IgG初次抗体反应存在缺陷。我们现在将这些研究扩展到二次反应和T细胞非依赖性（TI）B细胞反应。给TNF - LTα缺陷小鼠注射TD抗原SRBC不会诱导脾脏生发中心的形成。与形态学缺陷相关的是，TNF - LTα缺陷小鼠对TD抗原的IgG抗体反应存在缺陷，并且出现二次高IgM反应。TNF - LTα缺陷小鼠对TI抗原2型二硝基苯基 - 丙氨酰 - 甘氨酰 - 甘氨酰 - 聚蔗糖（DNP - alanyl - glycyl - glycyl - Ficoll）的反应基本缺失，而对TI抗原1型三硝基苯基 - 脂多糖（TNP - LPS）的反应仅IgG2b同种型显著降低。将野生型小鼠的骨髓细胞移植到经辐射的TNF - LTα缺陷小鼠中可恢复脾脏生发中心的形成，并纠正对TD和TI抗原的IgM和IgG反应。这些数据表明，TNF和/或LTα信号传导对于生发中心的形成以及对TD和TI型2抗原的IgM和IgG反应至关重要。
