Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells.
Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells.
复制标题
金黄色葡萄球菌蛋白A A破坏了由长寿命的浆细胞介导的免疫力。
DOI：
10.4049/jimmunol.1600093
复制
发表时间：
2017-02-01
期刊：
影响因子：
--
通讯作者：
Vilen BJ
中科院分区：
文献类型：
--
作者：
Keener AB;Thurlow LT;Kang S;Spidale NA;Clarke SH;Cunnion KM;Tisch R;Richardson AR;Vilen BJ
金黄色葡萄球菌感染不会引起长期的保护性免疫，其原因尚不完全清楚。人类和鼠类疫苗研究支持抗体在防止反复感染方面发挥作用，但金黄色葡萄球菌通过葡萄球菌蛋白 A (SpA) 的表达来调节 B 细胞反应，这是一种表面蛋白，可驱动多克隆 B 细胞扩增并在没有共刺激的情况下诱导细胞死亡。在这项小鼠研究中，我们表明 SpA 通过增强短命滤泡外反应和减少骨髓 (BM) 驻留长寿命 PC (LLPC) 库来改变浆母细胞和浆细胞 (PC) 的命运。 LLPC 的缺失与抗原特异性、类别转换抗体的快速下降有关。相比之下，当先前接种的小鼠受到同基因 Δspa 金黄色葡萄球菌的攻击时，细胞在 BM 存活生态位中增殖并维持长期抗体滴度。 SpA 对 PC 命运的影响仅限于二次反应，因为在接种 WT 或 Δspa 金黄色葡萄球菌的小鼠的初次反应期间，抗体水平和 B 细胞记忆的形成正常发生。因此，未能建立针对金黄色葡萄球菌的长期保护性抗体滴度并不是 B 细胞记忆形成减弱的结果；相反，SpA 降低了进入 BM 的 PC 的增殖能力，从而减少了长寿命池中的细胞数量。
Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for antibodies in protecting against recurring infections, but S. aureus modulates the B cell response through expression of Staphylococcal Protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of co-stimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs (LLPCs). The absence of LLPCs was associated with a rapid decline in antigen-specific, class-switched antibody. In contrast, when previously inoculated mice were challenged with isogenic Δspa S. aureus, cells proliferated in the BM survival niches and sustained long-term antibody titers. The effects of SpA on PC fate were limited to the secondary response, as antibody levels and the formation of B cell memory occurred normally during the primary response in mice inoculated with either WT or Δspa S. aureus. Thus, failure to establish long-term protective antibody titers against S. aureus was not a consequence of diminished formation of B cell memory; instead, SpA reduced the proliferative capacity of PCs that entered the BM, diminishing the number of cells in the long-lived pool.