Nies J H, Bär C, Schlenvoigt G, Fahlbusch B, Zwacka G, Markert U R
Institute for Clinical Immunology, Friedrich-Schiller-University Jena, Germany.
J Investig Allergol Clin Immunol. 2002;12(2):99-106.
Cytokines play an important role in mediating immunoglobulin switch, the secretion of protective mucosal immunoglobulins, and the development of allergic diseases. This study investigates whether B cells from allergic and healthy children have different capacities to secrete immunoglobulins after stimulation with IL-4, IL-6, IL-10, IL-11, and IL13.
We analyzed the peripheral venous blood of 44 healthy probands and of 109 allergic patients with a mean age of 13 years, allergic to grass pollen, birch pollen, and house dust mites. Lymphocytes were isolated by a density gradient and B cells were enriched by using a Magnetic Activated Cell Separator (MACS) and anti-CD19 microbeads. B Cells were co-cultured with human CDw32 (Fc gammaRII) expressing mouse Ltk fibroblasts and mouse anti-human CD40 monoclonal antibodies (CD40 system). The interleukins IL-4, IL-6, IL-10, IL-11, and IL-13 were supplemented in various combinations. After 14 days, concentrations of IgE, IgG, IgA, and IgM were measured in the supernatants with ELISA.
Suppression of IgA-, IgG, and IgM- synthesis was induced by stimulation of B cells with IL-4. After additional application of IL-10, IgA, IgG, and IgM synthesis was significantly increased. When cultures stimulated with IL-4 were additionally supplemented with IL-10, IgA, and IgG synthesis of B cells obtained from allergic individuals was significantly decreased compared to nonallergic individuals. IgE-secretion of B cells from allergic individuals was significantly increased compared to nonallergic individuals after stimulation with IL-4.
Our results implicate that IL-4 is essential for the regulation of immunoglobulin class switch to IgE and that IL-4 is an important cytokine for the development of allergic diseases. The capacity of B cells in allergic children to produce less IgA and IgG in response to additional stimulation with IL-10 of cultures supplemented with IL-4 could play an important role in mediating a mucosal immune system vulnerable to allergens. This phenomenon could contribute to the pathogenesis of allergic diseases.
细胞因子在介导免疫球蛋白转换、保护性黏膜免疫球蛋白的分泌以及过敏性疾病的发展中起重要作用。本研究调查了过敏儿童和健康儿童的B细胞在受到白细胞介素-4（IL-4）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、白细胞介素-11（IL-11）和白细胞介素-13（IL-13）刺激后分泌免疫球蛋白的能力是否存在差异。
我们分析了44名健康受试者以及109名平均年龄为13岁、对草花粉、桦树花粉和屋尘螨过敏的过敏患者的外周静脉血。通过密度梯度分离淋巴细胞，使用磁性激活细胞分选仪（MACS）和抗CD19微珠富集B细胞。将B细胞与人表达CDw32（FcγRII）的小鼠Ltk成纤维细胞以及小鼠抗人CD40单克隆抗体（CD40系统）共同培养。以各种组合添加白细胞介素IL-4、IL-6、IL-10、IL-11和IL-13。14天后，用酶联免疫吸附测定法（ELISA）测量上清液中IgE、IgG、IgA和IgM的浓度。
用IL-4刺激B细胞可诱导IgA、IgG和IgM合成的抑制。额外添加IL-10后，IgA、IgG和IgM的合成显著增加。当用IL-4刺激的培养物中额外补充IL-10时，与非过敏个体相比，从过敏个体获得的B细胞的IgA和IgG合成显著降低。与非过敏个体相比，过敏个体的B细胞在受到IL-4刺激后IgE分泌显著增加。
我们的结果表明，IL-4对于免疫球蛋白类别转换为IgE的调节至关重要，并且IL-4是过敏性疾病发展的重要细胞因子。过敏儿童的B细胞在补充IL-4的培养物中受到IL-10额外刺激时产生较少IgA和IgG的能力，可能在介导易受过敏原影响的黏膜免疫系统中起重要作用。这种现象可能有助于过敏性疾病的发病机制。
