Jabara H H, Buckley R H, Roberts J L, Lefranc G, Loiselet J, Khalil G, Geha R S
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Blood. 1998 Oct 1;92(7):2435-40.
CD40 is a member of the tumor necrosis factor receptor family and plays an important role in B-cell survival, growth, differentiation, and isotype switching. Recently, CD40 has been shown to associate with JAK3, a member of the family of Janus Kinases, which are nonreceptor protein kinases involved in intracellular signaling mediated by cytokines and growth factors. To investigate the role of JAK3 in CD40-mediated signaling, we studied the effect of CD40 stimulation on B-cell proliferation, IgE isotype switching, and upregulation of surface expression of CD23, ICAM-1, CD80, and LT-alpha in JAK3-deficient patients. Our studies show that stimulation of B cells with monoclonal antibody to CD40 in the presence of interleukin-4 (IL-4) or IL-13 resulted in similar responses in JAK3-deficient patients and normal controls. This suggests that JAK3 is not essential for CD40-mediated B-cell proliferation, isotype switching, and upregulation of CD23, ICAM-1, CD80, and LT-alpha surface expression.
CD40是肿瘤坏死因子受体家族的一员，在B细胞的存活、生长、分化及同种型转换中发挥重要作用。最近研究表明，CD40与JAK3相关联，JAK3是Janus激酶家族的成员，属于非受体蛋白激酶，参与由细胞因子和生长因子介导的细胞内信号传导。为了研究JAK3在CD40介导的信号传导中的作用，我们研究了CD40刺激对JAK3缺陷患者B细胞增殖、IgE同种型转换以及CD23、ICAM-1、CD80和LT-α表面表达上调的影响。我们的研究表明，在白细胞介素-4（IL-4）或IL-13存在的情况下，用抗CD40单克隆抗体刺激B细胞，JAK3缺陷患者和正常对照产生相似反应。这表明JAK3对于CD40介导的B细胞增殖、同种型转换以及CD23、ICAM-1、CD80和LT-α表面表达上调并非必不可少。
