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首页> 外文期刊>Molecular and Cellular Biology >The BTB-kelch Protein KLHL6 Is Involved in B-Lymphocyte Antigen Receptor Signaling and Germinal Center Formation
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The BTB-kelch Protein KLHL6 Is Involved in B-Lymphocyte Antigen Receptor Signaling and Germinal Center Formation

机译：BTB kelch蛋白KLHL6参与B淋巴细胞抗原受体信号传导和生殖中心的形成

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摘要

BTB-kelch proteins can elicit diverse biological functions but very little is known about the physiological role of these proteins in vivo. Kelch-like protein 6 (KLHL6) is a BTB-kelch protein with a lymphoid tissue-restricted expression pattern. In the B-lymphocyte lineage, KLHL6 is expressed throughout ontogeny, and KLHL6 expression is strongly upregulated in germinal center (GC) B cells. To analyze the role of KLHL6 in vivo, we have generated mouse mutants of KLHL6. Development of pro- and pre-B cells was normal but numbers of subsequent stages, transitional 1 and 2, and mature B cells were reduced in KLHL6-deficient mice. The antigen-dependent GC reaction was blunted (smaller GCs, reduced B-cell expansion, and reduced memory antibody response) in the absence of KLHL6. Comparison of mutants with global loss of KLHL6 to mutants lacking KLHL6 specifically in B cells demonstrated a B-cell-intrinsic requirement for KLHL6 expression. Finally, B-cell antigen receptor (BCR) cross-linking was less sensitive in KLHL6-deficient B cells compared to wild-type B cells as measured by proliferation, Ca2+ response, and activation of phospholipase Cγ2. Our results strongly point to a role for KLHL6 in BCR signal transduction and formation of the full germinal center response.
机译：BTB-kelch蛋白可以引发多种生物学功能，但对于这些蛋白在体内的生理作用知之甚少。 Kelch-like蛋白6（KLHL6）是一种BTB-kelch蛋白，具有淋巴组织受限的表达模式。在B淋巴细胞谱系中，KLHL6在整个个体发育过程中表达，并且KLHL6表达在生发中心（GC）B细胞中强烈上调。为了分析KLHL6在体内的作用，我们产生了KLHL6的小鼠突变体。在KLHL6缺陷小鼠中，前B细胞和前B细胞的发育正常，但随后阶段，过渡1和2以及成熟B细胞的数量减少。在不存在KLHL6的情况下，抗原依赖性GC反应变钝（较小的GC，减少的B细胞扩增和降低的记忆抗体反应）。 KLHL6整体缺失的突变体与B细胞中缺少KLHL6的突变体的比较证明了KLHL6表达的B细胞内在要求。最后，通过增殖，Ca 2 + 应答和磷脂酶活化，与野生型B细胞相比，KLHL6缺陷型B细胞中的B细胞抗原受体（BCR）交联敏感性较低。 Cγ2。我们的结果强烈指出KLHL6在BCR信号转导和完整生发中心反应形成中的作用。

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