EXPRESSION AND FUNCTION OF THE INTERLEUKIN-7 RECEPTOR IN MURINE LYMPHOCYTES

EXPRESSION AND FUNCTION OF THE INTERLEUKIN-7 RECEPTOR IN MURINE LYMPHOCYTES
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DOI:
10.1073/pnas.90.19.9125
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发表时间:
1993-10-01
影响因子:
11.1
通讯作者:
NISHIKAWA, SI
NISHIKAWA, SI
中科院分区:
综合性期刊1区
文献类型:
--
作者:
SUDO, T;NISHIKAWA, S;NISHIKAWA, SI

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已生产出一种单克隆抗体 A7R34,它可识别高亲和力白细胞介素 7 受体 (IL-7Ra) 并阻断 IL-7 和 IL-7Ra 之间的结合。 A7R34 细胞表面染色表明 IL-7Ra 在 B 细胞和 T 细胞谱系中均表达。在骨髓中,不表达表面 IgM 的未成熟 B 谱系细胞为 IL-7Ra+。在胸腺中,在 CD4-8- T 细胞以及 CD4 或 CD8 单阳性细胞中检测到 IL-7Ra,但在 CD4+8+ 双阳性细胞中未检测到。在外周淋巴组织中,CD4和CD8单阳性细胞是表达IL-7Ra的主要细胞类型。在长期 B 前体细胞培养物中添加 A7R34 可抑制 B 谱系细胞的增殖,表明 IL-7 是体外 B 细胞发生的绝对必要条件。与体外结果一致,向成年小鼠连续注射 A7R34 导致 B 前体细胞和胸腺细胞减少,而外周组织中相当一部分成熟 B 和 T 细胞在实验的 2 周内持续存在。当从妊娠第14天开始注射A7R34时,有可能产生缺乏B细胞的小鼠。这些结果表明,IL-7 是分别在小鼠骨髓和胸腺中生成 B 细胞和 T 细胞的必需分子。此外,IL-7Ra 将是调节这些过程的唯一受体系统。
A monoclonal antibody, A7R34, that recognizes the high-affinity interleukin 7 receptor (IL-7Ra) and blocks the binding between IL-7 and IL-7Ra has been produced. Cell surface staining with A7R34 demonstrated that IL-7Ra is expressed in both B- and T-cell lineages. In the bone marrow, immature B-lineage cells that do not express surface IgM were IL-7Ra+. In the thymus, IL-7Ra was detected in CD4-8- T cells and also in CD4 or CD8 single-positive cells but not in CD4+8+ double-positive cells. In the peripheral lymphoid tissues, both CD4 and CD8 single-positive cells were the major cell types that express IL-7Ra. Addition of A7R34 to a long-term B-precursor-cell culture inhibited proliferation of the B-lineage cells, indicating that IL-7 is an absolute requirement for in vitro B-cell genesis. Consistent with this in vitro result, continuous injection of A7R34 into an adult mouse resulted in a decrease of B-precursor cells and also of thymocytes, whereas a considerable fraction of mature B and T cells in the peripheral tissues persisted over 2 weeks of the experiment. When A7R34 injection is started from day 14 of gestation, it is possible to produce mice that lack B cells. These results indicate that IL-7 is an essential molecule for generation of both B and T cells in murine bone marrow and thymus, respectively. Moreover, IL-7Ra would be the sole receptor system regulating these processes.