ANALYSIS OF IMMUNOREGULATORY DEFECT IN MRL/LPR MICE

MRL/LPR 小鼠免疫调节缺陷分析

• 批准号: 3071304
• 负责人: Ann Marshak-Rothstein
• 金额: $ 6.6万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3071304
• 关键词: B lymphocyte; T lymphocyte; antiantibody; antibody formation; autoantibody; autoimmune disorder; autoradiography; bone marrow transplantation; cell transformation; clone cells; enzyme linked immunosorbent assay; flow cytometry; graft versus host disease; hematopoietic stem cells; histocompatibility antigens; hybridomas; immunogenetics; immunoglobulin G; immunoregulation; interleukin 2; interleukin 3; leukocyte activation /transformation; leukocyte disorder; leukopoiesis; mixed lymphocyte reaction test; monoclonal antibody; nephritis; newborn animals; radiation immunosuppression; radioimmunoassay; receptor; rheumatoid factor; spleen transplantation; splenectomy; systemic lupus erythematosus; tissue mosaicism

MRL/1 mice have an unusal stem cell defect that can manifest itself, depending on conditions, in either a lymphoproliferative lupus-like syndrome or in a runting graft-versus-host syndrome. Autoimmunity is associated with production of many auto- antibody specificities including exceptionally high titers of anti- IgG antibody, referred to as rheumatoid factors (RF). The proposed study addressed 4 main questions pertaining to the MRL/1 model: 1) What factors are necessary are sufficent for the massive T cell lymphoproliferation characteristic of MRL/1 mice and how does this autoimmune environment affect the differentiation of normal stem cells; 2) What are the target and effector cells involved in the MRL/1 runting syndrome; 3) What elicits RF production in MRL/1 mice and how do RF regulate other B cells and influence disease progression; and 4) What is the role of somatic muation in the generation of autoantibodies? To approach these issues, "autoimmune x normal" chimeric mice will be produced in which a mixture of phenotypically distinct normal and autoimmune stem cells mature together in various kinds of autoimmune environments. B cell activity will be monitored by measuring serum Ig and autoantibody titers. T cell functional activity will be measured in limiting dilution cultures. The RF studies will involve the production and analysis of monoclonal RF derived from MRL/1 and MRL/1 backcross mice. Somatic mutation will be assessed by determining the rate and direction of diversification of a particular germline gene following antigen stimulation in an autoimmune environment. Overall these studies should contribute to our basic understanding of immunoregulatory pathways. The results of this proposal should eventually have clinical application with regard to the control of autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis as well as certain forms of graft-versus-host disease.

MRL/1小鼠有一种不寻常的干细胞缺陷，可以表现出来

项目成果

Autoantibody in MRL/Mp-lpr/lpr mice. A monoclonal antibody specific for the abnormal T cells from mice bearing the lpr/lpr gene.

MRL/Mp-lpr/lpr 小鼠中的自身抗体。

• 发表时间: 1989
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Yamada,K;Spezialetti,R;Marshak-Rothstein,A;Sy,MS
• 通讯作者: Sy,MS

Resistance to lymphoid engraftment in lpr recipients of normal bone marrow: characterization of chimeric stem cell, monocyte and peripheral lymphoid lineages.

正常骨髓 lpr 受体对淋巴移植的抵抗力：嵌合干细胞、单核细胞和外周淋巴谱系的特征。

• DOI: 10.1002/eji.1830200908
• 发表时间: 1990
• 期刊: European journal of immunology
• 影响因子: 5.4
• 作者: Glaser,RM;Marshak-Rothstein,A
• 通讯作者: Marshak-Rothstein,A