CD98hc facilitates B cell proliferation and adaptive humoral immunity.

CD98hc facilitates B cell proliferation and adaptive humoral immunity.
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DOI:
10.1038/ni.1712
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发表时间:
2009-04
期刊:
影响因子:
30.5
通讯作者:
--
中科院分区:
医学1区
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--
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抗原特异性淋巴细胞的增殖和由此产生的克隆扩张对于适应性免疫至关重要。我们报告说,B 细胞特异性删除 CD98hc 会由于完全抑制 B 细胞增殖和随后的浆细胞形成而减少抗体反应。 CD98hc 的缺失不会损害早期 B 细胞激活,但会抑制 MAP 激酶 Erk1/2 的后期激活和 p27 细胞周期抑制剂的下调。用 CD98hc 突变体重建 CD98hc 缺陷型 B 细胞表明,对于 B 细胞增殖,CD98hc 的整合素结合结构域是必需的,但 CD98hc 的氨基酸转运功能是可有可无的。因此,CD98hc 支持整合素依赖性 B 细胞快速增殖。我们认为适应性免疫的优势有利于脊椎动物中 CD98hc 的出现。
Proliferation of antigen-specific lymphocytes and resulting clonal expansion is essential for adaptive immunity. We report that B cell-specific deletion of CD98hc reduced antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc didn’t impair early B cell activation, but did inhibit later activation of the MAP kinase Erk1/2 and down regulation of the p27 cell cycle inhibitor. Reconstitution of CD98hc-deficient B cells with CD98hc mutants revealed that the integrin-binding domain of CD98hc is required, but the amino acid transport function of CD98hc is dispensable, for B cell proliferation. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored appearance of CD98hc in vertebrates.
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