Xue Liquan, Morris Stephan W, Orihuela Carlos, Tuomanen Elaine, Cui Xiaoli, Wen Renren, Wang Demin
Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nat Immunol. 2003 Sep;4(9):857-65. doi: 10.1038/ni963. Epub 2003 Aug 10.
Bcl10 is an intracellular protein essential for nuclear factor (NF)-kappaB activation after lymphocyte antigen receptor stimulation. Using knockout mice, we show that absence of Bcl10 impeded conversion from transitional type 2 to mature follicular B cells and caused substantial decreases in marginal zone and B1 B cells. Bcl10-deficient B cells showed no excessive apoptosis. However, both Bcl10-deficient follicular and marginal zone B cells failed to proliferate normally, although Bcl10-deficient marginal zone B cells uniquely failed to activate NF-kappaB efficiently after stimulation with lipopolysaccharide. Bcl10-deficient marginal zone B cells did not capture antigens, and Bcl10-deficient (Bcl10-/-) mice failed to initiate humoral responses, leading to an inability to clear blood-borne bacteria. Thus, Bcl10 is essential for the development of all mature B cell subsets.
Bcl10是一种细胞内蛋白，在淋巴细胞抗原受体刺激后对核因子（NF）-κB激活至关重要。利用基因敲除小鼠，我们发现缺乏Bcl10会阻碍过渡2型B细胞向成熟滤泡B细胞的转化，并导致边缘区B细胞和B1 B细胞显著减少。Bcl10缺陷型B细胞未表现出过度凋亡。然而，Bcl10缺陷型滤泡B细胞和边缘区B细胞均无法正常增殖，尽管Bcl10缺陷型边缘区B细胞在用脂多糖刺激后独特地无法有效激活NF-κB。Bcl10缺陷型边缘区B细胞无法捕获抗原，Bcl10缺陷（Bcl10-/-）小鼠无法启动体液免疫反应，导致无法清除血源细菌。因此，Bcl10对所有成熟B细胞亚群的发育至关重要。
