FUNCTION OF CD19 IN B CELL DEVELOPMENT & DIFFERENTIATION
FUNCTION OF CD19 IN B CELL DEVELOPMENT & DIFFERENTIATION
批准号:
2637332
负责人:
ROBERT C RICKERT
金额:
$17.58万
依托单位国家:
美国
项目类别:
财政年份:
1998
资助国家:
美国
项目状态:
已结题
起止时间:
1998-04-01 至 2003-03-31
中文摘要
描述(改编自研究者摘要):抗原
英文摘要
DESCRIPTION (Adapted from the Investigator's Abstract): Antigen
receptor-mediated signaling is the key determinant governing B lymphocyte
activation, differentiation or death. Molecules that modulate signals
through the B cell receptor (BCR) can thus be instrumental in determining B
cell fate. Much attention has been given to intracellular intermediates
acting downstream of the BCR. This proposal addresses the biological role
of the B cell "co-receptor" CD19 which, in the appropriate context, can
augment BCR-mediated B cell activation and proliferation. The investigator
has found that CD19--deficient mice are impaired in B cell lymphopoiesis and
in responding to T cell-dependent antigens, and he proposes to determine the
molecular basis for these defects in the context of CD19 association with
the BCR and the CD19/CD21 (complement receptor 2)/CD81 complexes. In Aim 1
the role of CD19 in early B cell development will be examined, focusing on
developmental checkpoints regulated by pre-BCR or BCR signaling. This
involves a comparative analysis of CD19-/- and wildtype mice, which will be
refined by the use of pre-BCR mutant mice and immunoglobulin transgenic mice
bred onto the CD19 null background. As CD19-/- mice exhibit a severe
reduction in B-1 (formerly ly-1) B cells, in Aim 1b they will determine
whether this deficiency is mainly attributed to inefficient generation,
expansion or maintenance of this important subpopulation of B cells. Aim 2
addresses the role of CD19 in the recognition of and activation by foreign
antigen. It will be determined whether CD19 acts as the signaling moiety of
the CD19/CD21/CD81 complex, which is known to synergize with surface
immunoglobulin in the co-recognition of opsonized (C3d-bearing) foreign
antigen. Immunizations will be accompanied by flow cytometric and
immunohistochemical techniques to assess B cell differentiation, migration
and survival. Aim 3 will delineate the dual roles of CD19 as both a member
of the CD19/CD21/CD81 complex and also as an elementary component of the
BCR. This will be accomplished by complementation of the CD19 null mutation
with transgenes encoding modified CD19 molecules which associate exclusively
with the BCR or CD19/CD21/CD81 complexes. This genetic approach will assess
the relative contribution of CD19 to the function of these crucial signaling
complexes in effecting B cell differentiation and antibody production.
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资助金额:$22.91万
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Follicular dendritic cells and B cell tolerance
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资助金额:$29.25万
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财政年份:2012
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Functional Antagonists of EBI12/GPR183 as chemical probes for inflammation
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批准号:8328179
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资助金额:$4.88万
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财政年份:2012
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Elucidating IKK1 function in germinal center B cell differentiation
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批准号:8053310
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资助金额:$19.1万
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财政年份:2010
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Elucidating IKK1 function in germinal center B cell differentiation
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资助金额:$33.43万
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财政年份:2010
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依托单位:
Functional distinctions of IgM vs. IgG-containing B cell receptors
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资助金额:$18.91万
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财政年份:2010
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Functional distinctions of IgM vs. IgG-containing B cell receptors
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资助金额:$33.43万
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财政年份:2010
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Inflammation-regulated microRNA in B cell lymphoma
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批准号:8076384
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资助金额:$34.77万
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财政年份:2008
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依托单位:
Modeling B cell Lymphoma in the Mouse
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批准号:8043584
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依托单位:
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依托单位:
Modeling B cell Lymphoma in the Mouse
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批准号:7474785
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资助金额:$47.75万
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财政年份:2008
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依托单位:
Modeling B cell Lymphoma in the Mouse
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依托单位:
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批准号:7597154
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资助金额:$47.75万
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财政年份:2008
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依托单位:
Inflammation-regulated microRNA in B cell lymphoma
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批准号:7674039
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资助金额:$35.85万
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财政年份:2008
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Regulation of plasma cell differentiation by PI3-kinase
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依托单位:
海外基金