AUTOIMMUNE REACTIONS IN AGING

本申请提出了我们的总体计划，以调查 自身抗体增加的细胞和分子基础 老老鼠的回答 第一个目的是了解自身抗体的细胞基础 老老鼠的生产 增加的自发生产 自身抗体由传统的，非自身免疫性，非免疫性老年人 小鼠与分布的显著变化相关 淋巴细胞。 我们发现腹膜细胞数量增加， Ly 1携带的B细胞，以及低密度的活化淋巴细胞， 老老鼠 这些淋巴细胞群的贡献， 老年小鼠自身抗体的产生增加， 研究了 第二个目标是确定是否长寿命的外周T细胞 负责选择自身抗体 B细胞库。 已经发现，自体抗- 独特型抗体，一种在较大的 与年轻小鼠相比， 老年小鼠的外周血T细胞 这些细胞似乎选择了B 这种特异性的细胞在没有抗原的情况下， 通过独特型-反独特型相互作用。 的作用 老年小鼠外周血T细胞对B细胞的选择作用 对红细胞、甲状腺球蛋白、DNA自身抗体具有特异性 和免疫球蛋白进行研究。 第三个目的是检查免疫球蛋白的利用率 自身抗体重链可变区（VH）基因家族 在年老的老鼠身上形成细胞。 增加的激活和 在老年小鼠中发现的携带Ly 1的B细胞与在 新生小鼠，因为增加的代表性， 自身抗体，自身抗独特型抗体多反应性 抗体和在B内具有高“连接性”的抗体 细胞库 最近，胎儿和新生小鼠已经被 发现优先利用最D-近端VH基因 家庭 重链可变区基因的利用 一般来说，来自老年小鼠的B细胞和自身抗体产生的 将特别测定来自老年小鼠的B细胞。

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.