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THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS

THYMIC B CELL ACTIVATION IN MYASTHENIA GRAVIS
重症肌无力的胸腺 B 细胞激活
批准号:
3399628
负责人:
ARNOLD I LEVINSON
金额:
$16.31万
依托单位:
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

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中文摘要
翻译
尽管胸腺通常不被认为是B细胞的聚集地
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
  • 批准号:
    7179280
  • 项目类别:
  • 资助金额:
    $34.36万
  • 财政年份:
    2006
  • 负责人:
    ARNOLD I LEVINSON
  • 依托单位:
B Cell Superantigen Immune Complex Tissue Inflammation
  • 批准号:
    7106258
  • 项目类别:
  • 资助金额:
    $35.33万
  • 财政年份:
    2006
  • 负责人:
    ARNOLD I LEVINSON
  • 依托单位:
B Cell Superantigen Immune Complex Tissue Inflammation
  • 批准号:
    7340459
  • 项目类别:
  • 资助金额:
    $33.76万
  • 财政年份:
    2006
  • 负责人:
    ARNOLD I LEVINSON
  • 依托单位:
Intrathymic Pathogenesis of Myasthenia Gravis
  • 批准号:
    6603397
  • 项目类别:
  • 资助金额:
    $31.7万
  • 财政年份:
    2001
  • 负责人:
    ARNOLD I LEVINSON
  • 依托单位:
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