Mohr Elodie, Serre Karine, Manz Rudolf A, Cunningham Adam F, Khan Mahmood, Hardie Deborah L, Bird Roger, MacLennan Ian C M
Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom.
J Immunol. 2009 Feb 15;182(4):2113-23. doi: 10.4049/jimmunol.0802771.
IL-6 and APRIL influence the growth, differentiation, and survival of normal and neoplastic Ab-forming cells (AFC). In this study, we identify two subsets of myeloid cells that associate with the AFC and are the main producers of these factors during a T-dependent Ab response to alum-precipitated protein in mouse lymph nodes. First CD11c(+)CD8alpha(-) dendritic cells located in the perivascular area of the T zone provide about half of the IL-6 mRNA produced in the node together with significant amounts of APRIL mRNA. The number of these cells increases during the response, at least in part due to local proliferation. The second subset comprises Gr1(+)CD11b(+)F4/80(+) monocyte/macrophages. These colonize the medullary cords during the response and are the other main IL-6 mRNA producers and the greatest source of APRIL mRNA. This medullary cord monocyte/macrophage subset results in local increase of APRIL mRNA that mirrors the polarity of CXCL12 expression in the node. The distribution of these myeloid cell subsets correlates with a gradient of AFC maturation assessed by progressive loss of Ki67 as AFC pass from the B cell follicle along the perivascular areas to the medullary cords.
白细胞介素-6（IL-6）和增殖诱导配体（APRIL）影响正常和肿瘤性抗体形成细胞（AFC）的生长、分化及存活。在本研究中，我们鉴定出了与AFC相关的两个髓样细胞亚群，它们是小鼠淋巴结中对明矾沉淀蛋白的T细胞依赖性抗体应答过程中这些因子的主要产生者。首先，位于T区血管周围区域的CD11c(+)CD8α(-)树突状细胞产生了淋巴结中约一半的IL-6信使核糖核酸（mRNA）以及大量的APRIL mRNA。在应答过程中，这些细胞的数量增加，至少部分是由于局部增殖。第二个亚群由Gr1(+)CD11b(+)F4/80(+)单核细胞/巨噬细胞组成。这些细胞在应答过程中定位于髓索，是另一个主要的IL-6 mRNA产生者以及APRIL mRNA的最大来源。这个髓索单核细胞/巨噬细胞亚群导致APRIL mRNA在局部增加，这反映了淋巴结中趋化因子CXCL12表达的极性。这些髓样细胞亚群的分布与通过AFC从B细胞滤泡沿着血管周围区域到髓索的过程中Ki67的逐渐丧失所评估的AFC成熟梯度相关。
