B CELL TRANSFUSIONS FOR POSTBMT IMMUNE DEFICIENCY

B 细胞输注治疗 TBMT 后免疫缺陷

• 批准号: 2895387
• 负责人: JAN STOREK
• 金额: $ 9.35万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-10 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2895387
• 关键词: B lymphocyte; antibody; blood cell count; bone marrow transplantation; enzyme linked immunosorbent assay; flow cytometry; graft versus host disease; hemophilia As; human subject; humoral immunity; immune tolerance /unresponsiveness; immunodeficiency; immunoglobulin G; immunologic assay /test; leukocyte transfusion; life cycle; postoperative state; statistics /biometry; tissue /cell culture; tissue donors

DESCRIPTION: (Applicant's Abstract) The applicant's broad objective is to decrease the infectious morbidity and mortality of long-term marrow transplant survivors and, at the same time, to provide insight into the physiology of immune memory. The part of the application leading to clinical outcome: Patients undergoing bone marrow transplantation are immunodeficient for at least one year after grafting due in part to the lack of B cells. The applicant desires to attempt to improve these patients' humoral immunity by providing them with B cells from their marrow donors at one to two months after grafting. The work is divided into 4 steps: (1) Work out the large scale separation of B cells from donor blood. (2) Establish the safety of transfusions of the enriched B cells. (3) Perform a pilot prospective randomized trial comparing the responsiveness to vaccines in B cell-transfused vs. control patients. (4) If the pilot results are encouraging, perform a definitive large prospective randomized trial comparing the number and severity of infections in B cell-transfused vs. control patients. In this application, support is requested only for steps (1)-(3). The part of the application leading to immunologic information: This application also seeks to determine (A) the approximate life span of naive and memory B cell clones following infusion into human beings, and (B) whether long-term antibody production is due to periodic differentiation of B cells into plasma cells or due to long-lived plasma cells. (A) To define the approximate life span of naive and memory B cell clones, serial measurements of the mounts of naive and memory B cells will be performed in both the B cell-transfused and control patients. The longer the life span of a particular B cell subpopulation, the longer after the transfusions should the B cell transfused patients have higher blood counts of this subpopulation compared to the controls. Therefore, the time period from transfusing B cells to the last time point at which significantly higher naive or memory B cell counts are detected in the B cell-transfused vs. the control patients will be called the approximate life span of the naive or memory B cell clones. (B) At the same time, the patients will be used to find out whether the long-term production of antibodies to recall antigens like smallpox virus is mediated through smallpox-specific B cells some of which periodically differentiate into plasma cells or by long smallpox-specific plasma cells. Compared to the controls, the B cell transfused patients will have received substantially more B cells but the same amount of plasma cells. Therefore, if several months after the B cell transfusion the B cell transfused patients have higher serum levels of smallpox IgG, it will be assumed that B cells rather than long lived plasma cells are responsible for the long term IgG production, and vice versa.

描述：（申请人的摘要）申请人的广泛目标是 降低长期骨髓移植感染的发病率和死亡率 与此同时，她的阴道口也开始慢慢地湿润起来。 免疫记忆生理学 申请的一部分导致 临床结果：接受骨髓移植的患者 移植后至少一年免疫缺陷，部分原因是 缺乏B细胞。 申请人希望尝试改进这些 患者的体液免疫，通过提供他们的B细胞， 移植后一到两个月的骨髓捐赠者。 工作分工 分为4个步骤：（1）进行B细胞的大规模分离， 捐献者的血 (2)建立输血的安全性， B细胞。 (3)进行一项前瞻性随机试验， B细胞输注患者与对照患者对疫苗的反应性。 (4)如果试点结果令人鼓舞， 一项前瞻性随机试验， 在B细胞输注与对照患者中的感染。 在这 申请时，只要求对步骤（1）-（3）提供支持。 的部分 导致免疫学信息的应用：该应用 也试图确定（A）天真的近似寿命， 输注到人中后的记忆B细胞克隆，和（B） 长期抗体产生是否是由于周期性分化 B细胞转化为浆细胞或浆细胞寿命长。 (A)到 定义初始和记忆B细胞克隆的近似寿命， 将连续测量幼稚和记忆B细胞的数量， 在B细胞输注患者和对照患者中进行。 的 特定B细胞亚群的寿命越长， 输血后B细胞输注患者应具有较高的 与对照组相比，该亚群的血细胞计数。因此，我们认为， 从使用B细胞接种到最后一个时间点的时间段， 在正常对照组中检测到显著更高的幼稚或记忆B细胞计数， 输注B细胞的患者与对照患者将被称为 初始或记忆B细胞克隆的近似寿命。 (B)在 同时，患者将被用来找出是否长期 产生抗体来回忆像天花病毒这样的抗原， 通过天花特异性B细胞介导， 分化为浆细胞或通过长的天花特异性血浆 细胞 与对照组相比，输注B细胞的患者将 接受了更多的B细胞，但血浆量相同 细胞 因此，如果在B细胞输注后几个月， B细胞输注患者血清天花IgG水平较高， 将假设B细胞而不是长寿的浆细胞是 负责长期IgG的产生，反之亦然。

项目成果

Low B-cell and monocyte counts on day 80 are associated with high infection rates between days 100 and 365 after allogeneic marrow transplantation

• DOI: 10.1182/blood.v96.9.3290.h8003290_3290_3293
• 发表时间: 2000-11-01
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Storek, J;Espino, G;Maloney, D
• 通讯作者: Maloney, D

Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic graft-versus-host disease

• DOI: 10.1182/blood.v90.12.4705.4705_4705_4709
• 发表时间: 1997-12-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Storek, J;Gooley, T;Appelbaum, FR
• 通讯作者: Appelbaum, FR

Improved Reconstitution of CD4 T Cells and B Cells But Worsened Reconstitution of Serum IgG Levels After Allogeneic Transplantation of Blood Stem Cells Instead of Marrow

同种异体移植造血干细胞而非骨髓后，CD4 T 细胞和 B 细胞的重建得到改善，但血清 IgG 水平的重建恶化

• 发表时间: 1997
• 作者: J. Storek;R. Witherspoon;D. Maloney;T. Chauncey;R. Storb
• 通讯作者: R. Storb

Kinetics of B, CD4 T, and CD8 T cells infused into humans: estimates of intravascular:extravascular ratios and total body counts.

注入人体的 B、CD4 T 和 CD8 T 细胞的动力学：血管内：血管外比率和总体计数的估计。

• DOI: 10.1006/clim.2001.5174
• 发表时间: 2002
• 期刊: Clinical immunology (Orlando, Fla.)
• 作者: Storek,Jan;Lalovic,BojanB;Rupert,Kate;Dawson,MonjaA;Shen,DannyD;Maloney,DavidG
• 通讯作者: Maloney,DavidG

Normal anti-CD3-stimulated proliferation of CD4 T cells at one year after allogeneic marrow transplantation.

同种异体骨髓移植后一年，抗 CD3 刺激的 CD4 T 细胞正常增殖。

• DOI: 10.1016/s0966-3274(99)80029-x
• 发表时间: 1999
• 期刊: Transplant immunology
• 影响因子: 1.5
• 作者: Storek,J;Dawson,MA;Maloney,DG
• 通讯作者: Maloney,DG