Impaired CD40-signalling in CD19-deficient mice selectively affects Th2-dependent isotype switching
Impaired CD40-signalling in CD19-deficient mice selectively affects Th2-dependent isotype switching
复制标题
DOI：
10.1046/j.1365-3083.2001.00824.x
复制
发表时间：
2001-01-01
影响因子：
3.7
通讯作者：
Lycke, NY
中科院分区：
文献类型：
--
作者：
Gärdby, E;Chen, XJ;Lycke, NY
B淋巴细胞的激活涉及抗原与特定受体的结合和通过几个膜辅助受体传递信号，其中CD19被发现起着关键的反应调节作用。虽然先前在CD19基因敲除小鼠中的研究表明，在缺乏这种辅助受体的情况下，对T细胞依赖的抗原的抗体反应会受到强烈的损害，但对于CD19缺陷对T细胞和B细胞之间相互作用的影响还知之甚少。在此，我们报道了CD19缺陷小鼠的Th2协调B细胞分化在黏膜或系统免疫反应中或在感染巴西拟青霉肠道感染后受到选择性损害。免疫球蛋白(Ig)G1或Ig E抗体反应低或无，Ig G2a反应正常。这种选择性缺陷不是由于CD19缺陷小鼠的Th2发育不良或白介素4反应不良造成的。相反，这是Th2-B细胞相互作用受损的结果，这是由于CD19缺陷的B细胞通过CD40发出信号的能力大大降低。因此，我们对CD19缺陷小鼠的研究表明，CD40L-CD40-相互作用对Th2比Th1协调的B细胞分化更重要。
Activation of B lymphocytes involves binding of antigen to the specific receptor and signalling through several membrane coreceptors, of which CD19 has been found to play a pivotal role as a response regulator. Although previous studies in CD19 gene knockout mice have demonstrated that antibody responses to T-cell-dependent antigens are strongly impaired in the absence of this coreceptor, little is known about the consequences of CD19 deficiency for the interaction between T and B cells. Here we report that Th2 coordinated B-cell differentiation is selectively impaired in CD19-deficient mice in response to mucosal or systemic immunizations or following an intestinal infection with Nippostrongylus brasiliensis. Whereas immunoglobulin (Ig)G1 or IgE antibody responses were low or absent, IgG2a responses were normal. The selective defect was not caused by a poor Th2-development or interleukin (IL)-4 responsiveness in CD19-deficient mice. Rather, it was the result of an impaired Th2-B cell interaction, owing to a substantially reduced ability to signal via CD40 in CD19-deficient B cells. Thus, our study in CD19-deficient mice suggests that CD40L-CD40-interactions are more important for Th2 than for Th1 co-ordinated B-cell differentiation.