A novel role for caveolin-1 in B lymphocyte function and the development of thymus-independent immune responses
A novel role for caveolin-1 in B lymphocyte function and the development of thymus-independent immune responses
复制标题
DOI：
10.4161/cc.5.16.3132
复制
发表时间：
2006-08-15
期刊：
影响因子：
4.3
通讯作者：
Lisanti, Michael P.
中科院分区：
文献类型：
--
作者：
Medina, Freddy A.;Williams, Terence M.;Lisanti, Michael P.
小窝蛋白-1(Cav-1)是许多参与信号转导的分子的支架或平台。然而，Cav-1在免疫系统中的表达和功能一直存在争议。在这里，我们证明了Cav-1mRNA和蛋白确实是以一种受调控的方式在小鼠B淋巴细胞中表达的，以响应内毒素。CAV-1基因缺陷小鼠的血清抗体水平降低。为了研究Cav-1在免疫球蛋白介导的免疫应答中的作用，我们用胸腺依赖和胸腺非依赖性抗原免疫野生型和Cav-1缺陷小鼠。我们的结果表明，Cav-1缺陷小鼠对胸腺依赖抗原有正常的反应，但对I型和II型胸腺非依赖性抗原的反应降低。但脾和腹膜的淋巴细胞数量没有改变，脾的结构也没有变化。小窝蛋白-1缺陷的B淋巴细胞在不同刺激条件下没有表现出明显的增殖变化。然而，我们发现Cav-1缺陷的B细胞在体外对内毒素的反应减少了免疫球蛋白G(3)的分泌。最后，我们还证明了人浆细胞(成熟的B淋巴细胞)在体内表达Cav-1。综上所述，这些结果为Cav-1在激活的B淋巴细胞中的表达提供了令人信服的证据，并证明了Cav-1在胸腺非依赖性免疫反应的发展中的作用。
Caveolin-1 (Cav-1) functions as a scaffold or platform for many molecules involved in signal transduction. However, the expression and function of Cav-1 in the immune system has been controversial. Here, we show that Cav-1 mRNA and protein is indeed expressed in murine B-lymphocytes in a regulated manner in response to LPS. Cav-1 deficient mice displayed reduced levels of antibody in their serum. In order to examine the role of Cav-1 in the development of immunoglobulin-mediated immune responses, we immunized wild-type and Cav-1 deficient mice with thymus-dependent and thymus independent antigens. Our results show that Cav-1 deficient mice have a normal response to thymus-dependent antigens, but have a reduced response to both type I and type II thymus independent antigens. However, lymphocyte populations in the spleen and peritoneum were not altered and no changes were observed in splenic architecture. Caveolin-1 deficient B-lymphocytes did not display altered proliferation in response to different stimuli. However, we found that Cav-1 deficient B cells have reduced IgG(3) secretion in vitro in response to LPS. Finally, we also demonstrate that human plasma cells ( mature B lymphocytes) express Cav-1 in vivo. Taken, together these results provide convincing evidence for the expression of Cav-1 in activated B-lymphocytes and demonstrate a role for Cav-1 in the development of thymus-independent immune responses.