Ketch-like protein 14 promotes B-1a but suppresses B-1b cell development
Ketch-like protein 14 promotes B-1a but suppresses B-1b cell development
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Kelch 样蛋白 14 促进 B-1a 但抑制 B-1b 细胞发育
DOI：
10.1093/intimm/dxy033
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发表时间：
2018-07-01
影响因子：
4.4
通讯作者：
Wang, Ji-Yang
中科院分区：
文献类型：
--
作者：
Li, Shuyin;Liu, Jun;Wang, Ji-Yang
B-1细胞是先天的b细胞群，产生天然抗体，为宿主防御的第一道防线作出贡献。B-1细胞有两个子集：B-1a和B-1b。B-1a细胞是多反应性和自身反应性天然IgM抗体的主要产生者，而B-1b细胞可以对t细胞非依赖性抗原产生特异性反应。尽管B-1a和B-1b细胞具有重要的功能意义，但关于是什么调节了这两个亚群的发育，我们知之甚少。我们发现kelch样蛋白14 （KLHL14）在B细胞中高水平表达，但仅在少数非淋巴组织中低水平表达。虽然缺乏KLHL14的小鼠在出生后立即死亡，但杂合子发育正常，外观上没有明显异常。杂合小鼠骨髓中b细胞的发育和脾脏中的成熟和活化不受影响。然而，与野生型（WT）小鼠相比，Klhl14杂合小鼠腹膜B-1a细胞数量明显减少，B-1b细胞数量明显增加。与此一致的是，用Klhl14-/-胎肝细胞重组的Rag1-/-小鼠腹腔中B-1a的减少更严重，B-1b细胞的增加更严重。在体内，KLHL14不影响B-1a和B-1b细胞的周转或凋亡。此外，Klhl14-/-胎肝中B-1祖细胞的比例和绝对数量与WT胎肝相似。这些结果表明，KLHL14促进了小鼠B-1a的发育。
B-1 cells are innate-like B-cell population and produce natural antibodies that contribute to the first line of host defense. There are two subsets of B-1 cells: B-1a and B-1b. B-1a cells are the main producer of poly-reactive and autoreactive natural IgM antibodies, whereas B-1b cells can respond specifically to T-cell-independent antigens. Despite the functional significance of B-1a and B-1b cells, little information is available about what regulates the development of these two subsets. We found that Kelch-like protein 14 (KLHL14) was expressed at high levels in B cells but only at low levels in a few non-lymphoid tissues. Although mice lacking KLHL14 died right after birth, the heterozygotes developed normally with no gross abnormalities by appearance. B-cell development in the bone marrow and maturation and activation in the spleen were not affected in the heterozygous mice. However, the number of peritoneal B-1a cells was significantly reduced while B-1b cells were increased in Klhl14 heterozygous mice compared with wild-type (WT) mice. Consistently, Rag1-/- mice reconstituted with Klhl14-/- fetal liver cells had a more severe reduction of B-1a and an increase of B-1b cells in the peritoneal cavity. KLHL14 did not affect the turnover or apoptosis of B-1a and B-1b cells in vivo. Moreover, Klhl14-/- fetal liver contained a similar proportion and absolute numbers of the B-1 progenitor cells as did WT fetal liver. These results suggest that KLHL14 promotes B-1a development in mice.