Veninga Henrike, Borg Ellen G F, Vreeman Kyle, Taylor Philip R, Kalay Hakan, van Kooyk Yvette, Kraal Georg, Martinez-Pomares Luisa, den Haan Joke M M
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Eur J Immunol. 2015 Mar;45(3):747-57. doi: 10.1002/eji.201444983. Epub 2015 Jan 14.
Ag delivery to specific APCs is an attractive approach in developing strategies for vaccination. CD169(+) macrophages in the marginal zone of the spleen represent a suitable target for delivery of Ag because of their strategic location, which is optimal for the capture of blood-borne Ag and their close proximity to B cells and T cells in the white pulp. Here we show that Ag targeting to CD169(+) macrophages in mice resulted in strong, isotype-switched, high-affinity Ab production and the preferential induction and long-term persistence of Ag-specific GC B cells and follicular Th cells. In agreement with these observations, CD169(+) macrophages retained intact Ag, induced cognate activation of B cells, and increased expression of costimulatory molecules upon activation. In addition, macrophages were required for the production of cytokines that promote B-cell responses. Our results identify CD169(+) macrophages as promoters of high-affinity humoral immune responses and emphasize the value of CD169 as target for Ag delivery to improve vaccine responses.
将抗原递送至特定抗原呈递细胞（APC）是开发疫苗接种策略的一种有吸引力的方法。脾脏边缘区的CD169（+）巨噬细胞是抗原递送的合适靶点，因为它们的战略位置有利于捕获血源性病原体，并且它们与白髓中的B细胞和T细胞紧密相邻。在这里，我们表明，在小鼠中靶向CD169（+）巨噬细胞的抗原导致强烈的、同种型转换的、高亲和力抗体产生，以及抗原特异性生发中心B细胞和滤泡辅助性T细胞的优先诱导和长期持续存在。与这些观察结果一致，CD169（+）巨噬细胞保留完整抗原，诱导B细胞的同源激活，并在激活后增加共刺激分子的表达。此外，巨噬细胞是促进B细胞反应的细胞因子产生所必需的。我们的结果确定CD169（+）巨噬细胞是高亲和力体液免疫反应的促进者，并强调CD169作为抗原递送靶点以改善疫苗反应的价值。
