The role of IL-5 for mature B-1 cells in homeostatic proliferation, cell survival, and Ig production
The role of IL-5 for mature B-1 cells in homeostatic proliferation, cell survival, and Ig production
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DOI：
10.4049/jimmunol.172.10.6020
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发表时间：
2004-05-15
影响因子：
4.4
通讯作者：
Takatsu, K
中科院分区：
文献类型：
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作者：
Moon, BG;Takaki, S;Takatsu, K
B-1细胞与传统的B-2细胞不同，其细胞表面标志、解剖位置和自我补充活性在先天免疫反应中发挥着重要作用。B-1细胞结构性地表达IL-5Rα链(IL-5Rα)，并在包括IL-5和内毒素在内的各种刺激下产生抗体产生细胞。在此，我们报道了IL-5/IL-5R系统在维持成熟B-1细胞的数量和大小以及功能方面起着重要作用。给野生型小鼠、T细胞耗竭小鼠或肥大细胞耗尽小鼠注射抗IL-5单抗，B-1细胞总数和细胞大小的减少程度与IL-5Rpha缺陷(IL-5Rpha(-/-))小鼠相似。细胞转移实验表明，在缺乏IL-5RA的情况下，野生型小鼠的B-1细胞存活和重组激活基因2诱导的小鼠的动态平衡增殖受到损害。IL-5刺激野生型B-1细胞，但不刺激IL-5RA(-/-)B-1细胞，可增强CD40的表达，并在抗CD40单抗刺激后增加IgM和IgG的产生。在IL-5Rpha(-/-)小鼠中，未观察到口服内毒素引起的粪便中IgA生成的增加。我们的结果阐明了IL-5在成熟B-1细胞的动态平衡增殖和存活以及在粘膜组织中产生IgA方面的作用。
B-1 cells, distinguishable from conventional B-2 cells by their cell surface marker, anatomical location, and self-replenishing activity, play an important role in innate immune responses. B-1 cells constitutively express the IL-5R alpha-chain (IL-5Ralpha) and give rise to Ab-producing cells in response to various stimuli, including IL-5 and LPS. Here we report that the IL-5/IL-5R system plays an important role in maintaining the number and the cell size as well as the functions of mature B-1 cells. The administration of anti-IL-5 mAb into wild-type mice, T cell-depleted mice; or mast cell-depleted mice resulted in reduction in the total number and cell size of B-1 cells to an extent similar to that of IL-5Ralpha-deficient (IL-5Ralpha(-/-)) mice. Cell transfer experiments have demonstrated that B-1 cell survival in wild-type mice and homeostatic proliferation in recombination-activating gene 2-deticient mice are impaired in the absence of IL-5Ra. IL-5 stimulation of wild-type B-1 cells, but not IL-5Ra(-/-) B-1 cells, enhances CD40 expression and augments IgM and IgG production after stimulation with anti-CD40 mAb. Enhanced IgA production in feces induced by the oral administration of LPS was not observed in IL-5Ralpha(-/-) mice. Our results illuminate the role of IL-5 in the homeostatic proliferation and survival of mature B-1 cells and in IgA production in the mucosal tissues.