AUTOIMMUNE REACTIONS IN AGING

此应用程序显示了我们调查 自身抗体升高的细胞和分子基础 老年小鼠的反应。 第一个目的是了解自身抗体的细胞基础。 在老年小鼠身上产生。自然产量的增加 由常规、非自身免疫、非免疫老年人产生的自身抗体 老鼠的分布与显著的变化有关 淋巴细胞的数量。我们发现腹膜细胞的数量增加了， 携带Ly1的B细胞和低密度活化的淋巴细胞 老老鼠。这些淋巴种群对人类健康的贡献 老年小鼠自身抗体的产生将会增加 学习。 第二个目标是确定长寿的外周T细胞 在老年小鼠中负责选择自身抗体 B细胞谱系。已有研究发现，自身抗体水平-- 独特型抗体，一种在更大的 与幼龄小鼠相比，老年小鼠的数量受 老年小鼠的外周T细胞。这些单元格似乎选择了B 在没有抗原的情况下，可能有这种特异性的细胞 通过独特型-反独特型相互作用。的作用 老年小鼠外周T细胞对B细胞的选择 针对红细胞、甲状腺球蛋白、DNA的自身抗体 并将对免疫球蛋白进行研究。 第三个目的是研究免疫球蛋白的利用。 自身抗体介导的重链可变区基因家族 在老年小鼠体内形成细胞。激活和激活的数量增加 在老年小鼠中发现的携带Ly1的B细胞与在 新生小鼠，就像增加的代表是 自身抗体、自身抗独特型抗体多反应 抗体和B组内具有高“连通性”的抗体 细胞谱系。最近，胚胎和新生小鼠已经被 发现优先利用最接近D的VH基因 家人。重链可变区基因的利用 通常是由老年小鼠的B细胞和产生自身抗体 特别是来自老年小鼠的B细胞将被确定。

This application presents our overall plan to investigate the cellular and molecular basis of the increased autoantibody response of old mice. The first aim is to understand the cellular basis of autoantibody production in old mice. The increased spontaneous production of autoantibodies by conventional, non-autoimmune, non-immunized old mice is associated with significant changes in the distribution of lymphocytes. We found increased numbers of peritoneal cells, Ly1-bearing B cells, and low density, activated lymphocytes in old mice. The contribution of these lymphoid populations to the increased production of autoantibodies by old mice will be studied. The second aim is to determine if long-lived peripheral T cells in old mice are responsible for the selection of the autoantibody B cell repertoire. It has been found that the level of autoanti- idiotypic antibody, one of the autoantibodies produced in greater quantity in old as compared to young mice, is regulated by peripheral T cells in old mice. These cells appear to select B cells of this specificity in the absence of antigen, perhaps through idiotype-anti-idiotypic interactions. The role of peripheral T cells from old mice on the selection of the B cells specific for autoantibodies to erythrocytes, thyroglobulin, DNA and immunoglobulin will be investigated. The third aim is to examine the utilization of the immunoglobulin heavy chain variable region (VH) gene families by autoantibody forming cells in old mice. The increased number of activated and Ly1-bearing B cells in old mice is similar to that found in neonatal mice, as is the increased representation of autoantibodies, autoanti-idiotypic antibodies multi-reactive antibodies and antibodies with high "connectivity" within the B cell repertoire. Recently, fetal and neonatal mice have been found to utilize preferentially the most D-proximal VH gene families. The utilization of heavy chain variable region genes by B cells, in general, from old mice and autoantibody producing B cells from old mice in particular will be determined.