THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
批准号:
3399628
负责人:
ARNOLD I LEVINSON
金额:
$16.31万
依托单位国家:
美国
项目类别:
财政年份:
1983
资助国家:
美国
项目状态:
已结题
起止时间:
1983-04-01 至 1989-03-31
中文摘要
尽管胸腺通常不被认为是B细胞的一个部位
活动,在重症肌无力(MG)中是一个突出的B细胞场景
回应。这一活动的突出表现是产生了抗AChR
抗体(抗AChR),可能反映胸腺内的免疫事件
在疾病的发病机制中很重要。有几个原因可以解释为什么
胸腺B细胞反应突出,尽管不一致。它们包括:1)
胸腺B细胞是一个特别活跃的群体,它可以
根据血液B细胞的表型特性来区分,2)
胸腺微环境对B细胞特别有利
3)胸腺B细胞经历了一定程度的
体内的分化可能是局部遇到的刺激的结果。
这份提案中描述的实验将有助于1)充分
描述这些不寻常的胸腺B细胞的表型特征;2)
这些细胞的体外功能与其表型的相关性
3)确定抗原特异性胸腺辅助T细胞的表型
细胞,从而阐明辅助者活动的发育阶段
在胸腺中获得;4)确定MG胸腺细胞是否构成
产生支持B细胞分化所需的可溶性因子和5)
在确定是否有AChR表达之前,确定胸腺群体的特征
这样的受体细胞为产生抗AChR提供了刺激。什么时候都行
有可能,我们将对MG胸腺细胞和
自体血细胞,2)对照组胸腺细胞。
实现上述目标的技术途径包括:细胞
用单抗和自动化流程进行亚集分析
流式细胞术和免疫荧光显微镜,亚群分级
亲和层析和流式细胞仪分选在几种体外细胞中的应用
培养系统,测定免疫球蛋白的酶联免疫吸附试验和放射免疫测定
分泌到培养上清液中。增加了对机制的了解
重症肌无力患者的胸腺B细胞异常反应可能会增强
我们对异常局部胸腺内免疫事件和
最终可能有助于澄清启动的机制,
疾病加重或延续疾病。
英文摘要
Although the thymus is not generally considered to be a site of B cell
activity, in myasthenia gravis (MG) it is a scene of prominent B cell
responses. This activity, which is highlighted by production of anti-AChR
antibody (anti-AChR), likely reflects intrathymic immune events that are
important in disease pathogenesis. Several reasons could account for the
prominent albeit incongruous thymic B cell responses. They include: 1)
thymic B cells are a particularly reactive population, one which can be
distinguished on the basis of phenotypic properties from blood B cells, 2)
the thymic microenvironment is particularly supportive of B cell
differentiation and 3) thymic B cells have undergone some degree of
differentiation in vivo perhaps as a result of locally encountered stimuli.
The experiments described in this proposal will help to 1) fully
characterize the phenotypic properties of these unusual thymic B cells; 2)
correlate in vitro function of these cells with their phenotypic
properties; 3) determine the phenotype of antigen specific thymic helper T
cells and thus elucidate the developmental stage at which helper activity
is acquired in the thymus; 4) determine if MG thymus cells constitutively
produce soluble factors required to support B cell differentiation and 5)
characterize the thymic populations expressing AChR prior to determining if
such receptor cells provide a stimulus for anti-AChR production. Whenever
possible, comparisons will be made between 1) MG thymic cells and
autologous blood cells, 2) thymic cells of control subjects.
Technical approaches to accomplish the above objectives include: cell
subset analysis with monoclonal antibodies along with automated flow
cytometry and immunofluorescence microscopy, subset fractionation by
affinity chromatography and FACS sorting for use in several in vitro cell
culture systems, and ELISA and radioimmunoassay for measurement of Ig
secreted into culture supernatants. Increased knowledge of the mechanisms
underlying the anomalous thymic B cell responses in MG will likely enhance
our understanding of aberrant local intrathymic immune events and
ultimately may help to clarify mechanisms responsible for initiation,
potentiation or perpetuation of disease.
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B Cell Superantigen Immune Complex Tissue Inflammation
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批准号:7179280
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项目类别:
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资助金额:$34.36万
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财政年份:2006
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负责人:ARNOLD I LEVINSON
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依托单位:
B Cell Superantigen Immune Complex Tissue Inflammation
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批准号:7106258
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项目类别:
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资助金额:$35.33万
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财政年份:2006
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负责人:ARNOLD I LEVINSON
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依托单位:
B Cell Superantigen Immune Complex Tissue Inflammation
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批准号:7340459
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项目类别:
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资助金额:$33.76万
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财政年份:2006
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负责人:ARNOLD I LEVINSON
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依托单位:
Intrathymic Pathogenesis of Myasthenia Gravis
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批准号:6603397
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项目类别:
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资助金额:$31.7万
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财政年份:2001
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负责人:ARNOLD I LEVINSON
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依托单位:
Intrathymic Pathogenesis of Myasthenia Gravis
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批准号:6511608
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项目类别:
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资助金额:$31.7万
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财政年份:2001
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负责人:ARNOLD I LEVINSON
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依托单位:
Intrathymic Pathogenesis of Myasthenia Gravis
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批准号:6362038
-
项目类别:
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资助金额:$30.12万
-
财政年份:2001
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负责人:ARNOLD I LEVINSON
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依托单位:
Intrathymic Pathogenesis of Myasthenia Gravis
-
批准号:6740884
-
项目类别:
-
资助金额:$31.7万
-
财政年份:2001
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负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:2263621
-
项目类别:
-
资助金额:$22.74万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:2431131
-
项目类别:
-
资助金额:$23.65万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:2714436
-
项目类别:
-
资助金额:$24.6万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B-CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:3399624
-
项目类别:
-
资助金额:$20.18万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B-CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:3399629
-
项目类别:
-
资助金额:$19.94万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:3399623
-
项目类别:
-
资助金额:$15.76万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:3399627
-
项目类别:
-
资助金额:$17.19万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:2263619
-
项目类别:
-
资助金额:$21.87万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B-CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:3399631
-
项目类别:
-
资助金额:$22.55万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B-CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:3399630
-
项目类别:
-
资助金额:$21.61万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B-CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:2263617
-
项目类别:
-
资助金额:$23.28万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
-
批准号:3399626
-
项目类别:
-
资助金额:$11.95万
-
财政年份:1983
-
负责人:ARNOLD I LEVINSON
-
依托单位:
TRAINING PROGRAM/RHEUMATIC DISEASES
-
批准号:2077777
-
项目类别:
-
资助金额:$10.47万
-
财政年份:1982
-
负责人:ARNOLD I LEVINSON
-
依托单位:
海外基金