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Studies on the B cell development and its microenvironment

Studies on the B cell development and its microenvironment
B细胞发育及其微环境的研究
批准号:
08670264
负责人:
INABA Muneo
金额:
$1.6万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (C)
财政年份:
1996
资助国家:
日本
项目状态:
已结题
起止时间:
1996 至 1997

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中文摘要
翻译
我们描述了胸腺中的B细胞祖细胞。虽然成熟的胸腺B细胞为sIg^+、B220^+,但胸腺中的CD 43 ^-、B祖细胞为sIg^-、B220^<med>+、CD 43 ^+。当通过PCR扩增来自分选的B细胞祖细胞的DNA时,大多数祖细胞显示重排的IG D-J和V-D-J模式。当从胸腺中纯化B细胞祖细胞并将其胸腺内注射到Ig同种异型不同受体中时,在胸腺中检测到携带供体型Igh 6的B细胞,但在外周中未检测到。由这些祖细胞产生的胸腺B细胞是CD 5 ^+细胞,尽管CD 5分子的表达范围很广。此外,从接种了B细胞祖细胞的胸腺纯化的B细胞能够在CD 40配体加IL-10的影响下分化为抗体形成细胞,并分泌具有供体Igh 6同种异型的IgM。将胸腺前体B细胞静脉注射给scid小鼠后,胸腺前体B细胞可分化为成熟的B细胞,静脉注射后胸腺中检测到的CD 5 ^+ B细胞百分比明显升高。注射组明显高于脾脏和淋巴结组。这些发现表明B细胞的表面表型可能受到微环境的影响。目的:阐明支持胸腺祖细胞B细胞、基质细胞分化的体外条件。在IL-7的存在下,胸腺基质细胞,而不是来自骨髓的基质细胞或胸腺细胞系,可以支持胸腺祖B细胞的分化。
英文摘要
We characterize B cell progenitors in the thymus. Though mature thymic B cells are sIg^+, B220^+, but CD43^-, B cell progenitors in the thymus were found to be sIg^-, B220^<med>, and CD43^+. Most progenitors showed rearranged Ig D-J and V-D-J patterns when DNA from sorted B cell progenitors was amplified by PCR,blotted and probed. When B cell progenitors were purified from the thymus and injected intrathymically into Igh-allotype disparate recipients, B cells bearing donor-type Igh6 were detected in the thymus but not in the periphery. Thymic B cells generated from these progenitors were CD5^+ cells, though there was a broad range of expression of CD5 molecules. Furthermore, B cells purified from thymus that had been inoculated with B cell progenitors were able to differentiate into antibody-forming cells under the influence of CD40 ligand plus IL-10, and secreted IgM with donor Igh6-allotype. When thymic progenitor B cells were intravenously injected into scid mice, thymic progenitor B cells can differentiate to mature B cells, and the percentage of CD5^+ B cells detected in the thymus after iv. injection was significantly higher than those in the spleen and lymph nodes. These findings indicate the possibility that the surface phenotye of B cells is influenced by the microenvironment. To clarify the in vitro condition that supports the differentiation of thymic progenitor B cells, stroma cells. In the presence of IL-7, thymic stroma cells, but not stroma cells from the bone marrow nor thymic cell lines, could support the differentiation of thymic progenitor B cells.
期刊论文(17)
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会议论文
H.Doi: "Pluripotent hemopoietic stem cells are c-kit<low" Proc.Natl.Acad.Sci.(USA). 94. 2513-2517 (1997)
H.Doi:“多能造血干细胞的 c-kit<低”Proc.Natl.Acad.Sci.(美国)。
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N.Nishio: "Changes in markers, reoeptors and adhesion molecules expressed on hemopoietic stem cells after a single irrjection of 5-fluorouracil." Stem cells. 14. 584-591 (1996)
N.Nishio:“单次注射 5-氟尿嘧啶后,造血干细胞上表达的标记物、受体和粘附分子发生变化。”
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K.Inaba: "High levels of a major histocompatibility complex II-self peptides complex on dendritic cells from the T cell area of LN." J.Exp.Med.186. 665-672 (1997)
K.Inaba:“来自 LN T 细胞区域的树突状细胞上存在高水平的主要组织相容性复合物 II-自身肽复合物。”
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Z.Lian: "Intrathymically injected hemopoietic stem cells can differetiate into all lineage cells in the thymus." Stem cells. 15. 430-436 (1997)
Z.Lian:“胸腺内注射的造血干细胞可以分化为胸腺中的所有谱系细胞。”
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14
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      2000
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      Grant-in-Aid for General Scientific Research (C)
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