TACI is required for the survival of short- and long-lived plasma cells.

IF 3.4 4区 医学 Q2 IMMUNOLOGY
Kenji Funakoshi, Takuya Koike, Wataru Ise, Yuki Tai, Masashi Narazaki, Atsushi Kumanogoh, Takeshi Inoue, Tomohiro Kurosaki
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Abstract

In a typical immune response, naïve B cells are activated, differentiated into short-lived plasma cells (SLPCs), and then matured into long-lived plasma cells (LLPCs) in the bone marrow. Among three TNF family receptors (BAFF-R, TACI, and BCMA), BAFF-R and BCMA are known to be crucial for the maintenance of naïve B cells and bone marrow LLPCs, respectively. In contrast, the function of TACI remains unclear, as analysis of global TACI knockout mice suggests the existence of two opposing roles in B and plasma cells. Here, to define the role of TACI during T cell-dependent (TD) immune responses in a B and plasma cell-intrinsic manner, we utilized adoptive transfer experiments employing B cells with a conditional TACI knockout. We show that B cell activation is apparently normal in the absence of TACI, while it is crucial for the expansion of IgM+ and IgG1+ SLPCs and maintenance of their resultant bone marrow LLPCs. Hence, our data suggest that the hyper-B cell activation seen in global TACI knockout mice could be due to an indirect control of BAFF levels or B cell extrinsic anomalies.

TACI是短寿命和长寿命浆细胞存活所必需的。
在典型的免疫反应中,naïve B细胞被激活,分化成短寿命浆细胞(SLPCs),然后在骨髓中成熟为长寿命浆细胞(LLPCs)。在三种TNF家族受体(BAFF-R、TACI和BCMA)中,已知BAFF-R和BCMA分别对naïve B细胞和骨髓llpc的维持至关重要。相比之下,TACI的功能尚不清楚,因为对全球TACI敲除小鼠的分析表明,TACI在B细胞和浆细胞中存在两种相反的作用。在这里,为了确定TACI在B细胞和浆细胞固有方式的t依赖性(TD)免疫应答中的作用,我们利用有条件敲除TACI的B细胞进行过继转移实验。我们发现,在没有TACI的情况下,B细胞的活化显然是正常的,而TACI对于IgM+和IgG1+ slpc的扩增以及由此产生的骨髓llpc的维持至关重要。因此,我们的数据表明,在全球TACI基因敲除小鼠中看到的超B细胞激活可能是由于BAFF水平的间接控制或B细胞外源性异常。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
International immunology
International immunology 医学-免疫学
CiteScore
9.30
自引率
2.30%
发文量
51
审稿时长
6-12 weeks
期刊介绍: International Immunology is an online only (from Jan 2018) journal that publishes basic research and clinical studies from all areas of immunology and includes research conducted in laboratories throughout the world.
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