Evidence that marginal zone B cells possess an enhanced secretory apparatus and exhibit superior secretory activity
Evidence that marginal zone B cells possess an enhanced secretory apparatus and exhibit superior secretory activity
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DOI：
10.4049/jimmunol.177.6.3791
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Brewer, Joseph W.
中科院分区：
文献类型：
--
作者：
Gunn, Kathryn E.;Brewer, Joseph W.
边缘区 B (MZB) 细胞是第一个在体内启动针对多糖封装 Ag 的抗体分泌的脾 B 细胞。这种快速的 MZB 细胞反应可以在体外重现，因为 LPS 处理可在短短 12 小时内诱导抗体分泌。相反，体外 LPS 处理脾滤泡 B (FOB) 细胞会在 2-3 天后产生抗体分泌。这些不同的反应动力学的基础尚不清楚。我们对静息和 LPS 刺激的小鼠 MZB 和 FOB 细胞进行了离体分析，发现 MZB 细胞表达更高水平的 LPS TLR 复合物 RP105/MD-1，并且比 FOB 细胞对低浓度的 LPS 做出反应。此外，增加 LPS 剂量不会加速 FOB 细胞转化为 Ab 分泌的动力学。静息细胞的超微结构分析表明，MZB 细胞中的粗面内质网比 FOB 细胞中的粗面内质网更丰富。此外，RT-PCR 和免疫印迹分析表明，许多内质网驻留分子伴侣和折叠酶在静息 MZB 细胞中的表达水平高于静息 FOB 细胞。尽管 LPS 刺激的 MZB 和 FOB 细胞都会增加这些因子的表达，但 MZB 细胞表现出更快速的增加，这与 Ab 分泌动力学加速和分泌 IgM 的每细胞输出更高相关。这些数据表明，MZB 细胞对 LPS 等细菌成分具有极高的敏感性，并准备好快速、稳定地产生抗体，这使得 MZB 细胞非常适合作为不道德免疫的前线防御者。
Marginal zone B (MZB) cells are the first splenic B cells to initiate Ab secretion against polysaccharide-encapsulated Ags in vivo. This swift MZB cell response can be reproduced in vitro as LPS treatment induces Ab secretion in as little as 12 h. Conversely, in vitro LPS treatment of splenic follicular B (FOB) cells results in Ab secretion after 2-3 days. The basis for these distinct response kinetics is not understood. We performed ex vivo analysis of resting and LPS-stimulated murine MZB and FOB cells and found that MZB cells express higher levels of the LPS TLR complex RP105/MD-1 and respond to much lower concentrations of LPS than do FOB cells. Furthermore, increasing doses of LPS do not accelerate the kinetics by which FOB cells transition into Ab secretion. Ultrastructural analysis of resting cells demonstrated that rough endoplasmic reticulum is more abundant in MZB cells than in FOB cells. Additionally, RT-PCR and immunoblot analyses revealed that numerous endoplasmic reticulum resident chaperones and folding enzymes are expressed at greater levels in resting MZB cells than in resting FOB cells. Although both LPS-stimulated MZB and FOB cells increase expression of these factors, MZB cells exhibit a more rapid increase that correlates with accelerated kinetics of Ab secretion and higher per cell output of secreted IgM. These data indicate that MZB cells are equipped for exquisite sensitivity to bacterial components like LPS and poised for rapid, robust Ab production, making MZB cells ideally suited as frontline defenders in Immoral immunity.