Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-1903, USA.
Blood. 2010 Apr 15;115(15):3051-7. doi: 10.1182/blood-2009-08-239145. Epub 2010 Feb 4.
The ability of plasmacytoid dendritic cells (pDCs) to promote plasma cell differentiation and immunoglobulin (Ig) secretion through the production of type I interferon and interleukin-6 has been well documented, although the role of additional factors, including tumor necrosis factor receptor-ligand interactions, has not been addressed. On stimulation with the Toll-like receptor ligand CpG (B type, 2006) we found that pDCs exhibit strong and stable expression of CD70, a tumor necrosis factor family ligand that binds to its receptor CD27 expressed on memory B cells and promotes plasma cell differentiation and Ig secretion. Using a pDC/B-cell coculture system, we found that CpG-stimulated pDCs can induce the proliferation of CD40L-activated human peripheral B cells and Ig secretion. This occurs independently of interferon and residual CpG, and requires physical contact between pDCs and B cells. CpG-stimulated pDCs can induce the proliferation of both naive and memory B cells, although Ig secretion is restricted to the memory subset. Blocking the interaction of CD70 with CD27 using an antagonist anti-CD70 antibody reduces the induction of B-cell proliferation and IgG secretion by CpG-stimulated pDCs. We have therefore identified CD70 as an important factor in the regulation of B-cell growth and differentiation by pDCs.
浆细胞样树突状细胞 (pDC) 通过产生 I 型干扰素和白细胞介素-6 促进浆细胞分化和免疫球蛋白 (Ig) 分泌的能力已得到充分证实，尽管其他因素（包括肿瘤坏死因子受体配体相互作用）的作用尚未得到解决。在受到 Toll 样受体配体 CpG（B 型，2006）的刺激后，我们发现 pDC 表现出强烈和稳定的 CD70 表达，CD70 是一种肿瘤坏死因子家族配体，与表达在记忆 B 细胞上的 CD27 受体结合，促进浆细胞分化和 Ig 分泌。使用 pDC/B 细胞共培养系统，我们发现 CpG 刺激的 pDC 可以诱导 CD40L 激活的人外周 B 细胞增殖和 Ig 分泌。这独立于干扰素和残留的 CpG 发生，需要 pDC 和 B 细胞之间的物理接触。CpG 刺激的 pDC 可以诱导幼稚和记忆 B 细胞的增殖，尽管 Ig 分泌仅限于记忆亚群。使用抗 CD70 抗体阻断 CD70 与 CD27 的相互作用，可减少 CpG 刺激的 pDC 诱导的 B 细胞增殖和 IgG 分泌。因此，我们已经确定 CD70 是 pDC 调节 B 细胞生长和分化的重要因素。
