Fernandez C, Möller G
J Exp Med. 1978 Mar 1;147(3):645-55. doi: 10.1084/jem.147.3.645.
Young mice of dextran high responder strains were found to be complete nonresponders to the alpha-1-6 epitope of dextran during 30-40 days after birth. They also failed to respond to thymus-dependent dextran-protein conjugates. Cells from young and adult mice were activated equally well to polyclonal antibody synthesis by the polyclonal B-cell-activating property of dextran. There was no age difference in the immune response to haptens conjugated to dextran, indicating that dextran can function as an efficient carrier also in young mice. Unresponsiveness could not be attributed to suppressor T cells or to a suppressive environment in young animals, as shown by transfer experiments, in which living or irradiated cells from young and adult mice were admixed in various ways and transferred to irradiated recipients of different ages. Cells from young mice did not affect response of adult cells (and the reverse), nor did the age of the irradiated recipient influence the response. When lymphocytes from young and adult mice were polyclonally activated in vitro by lipopolysaccharide, only cells from young mice failed to synthesize antibodies against the alpha-1-6 epitope of dextran, although they produced antibodies of all other specificities tested for. It was concluded that young animals fail to express immunoglobulins directed against the alpha-1-6 epitope during the first 30-40 days after birth. Since the mice possess the VH gene coding for antibodies against this particular epitope, it was concluded that the timing of V gene expression is regulated during development, possibly at the V-C gene translocation level.
研究发现,右旋糖酐高反应性品系的幼鼠在出生后30 - 40天内对右旋糖酐的α-1-6表位完全无反应。它们对胸腺依赖性右旋糖酐-蛋白质偶联物也无反应。通过右旋糖酐的多克隆B细胞激活特性,幼鼠和成鼠的细胞对多克隆抗体合成的激活效果相同。对与右旋糖酐偶联的半抗原的免疫反应不存在年龄差异,这表明右旋糖酐在幼鼠中也可作为有效的载体发挥作用。转移实验表明,无反应性不能归因于幼龄动物中的抑制性T细胞或抑制性环境,在这些实验中,将幼鼠和成鼠的活细胞或经辐射的细胞以各种方式混合,并转移到不同年龄的经辐射的受体中。幼鼠的细胞不影响成年细胞的反应(反之亦然),经辐射受体的年龄也不影响反应。当幼鼠和成鼠的淋巴细胞在体外被脂多糖多克隆激活时,只有幼鼠的细胞不能合成针对右旋糖酐α-1-6表位的抗体,尽管它们能产生针对所有其他测试特异性的抗体。得出的结论是,幼龄动物在出生后的前30 - 40天内不能表达针对α-1-6表位的免疫球蛋白。由于小鼠拥有编码针对该特定表位抗体的VH基因,因此得出结论,V基因表达的时间在发育过程中受到调控,可能在V-C基因易位水平。