Department of Immunology, University of Washington, Seattle, WA 98109
Department of Immunology, University of Washington, Seattle, WA 98109.
J Immunol. 2019 Oct 1;203(7):1715-1729. doi: 10.4049/jimmunol.1900549. Epub 2019 Sep 4.
Targeting Ags to the CD180 receptor activates both B cells and dendritic cells (DCs) to become potent APCs. After inoculating mice with Ag conjugated to an anti-CD180 Ab, B cell receptors were rapidly internalized. Remarkably, all B cell subsets, including even transitional 1 B cells, were programed to process, present Ag, and stimulate Ag-specific CD4 T cells. Within 24-48 hours, Ag-specific B cells were detectable at T-B borders in the spleen; there, they proliferated in a T cell-dependent manner and induced the maturation of T follicular helper (T) cells. Remarkably, immature B cells were sufficient for the maturation of T cells after CD180 targeting: T cells were induced in BAFFR mice (with only transitional 1 B cells) and not in μMT mice (lacking all B cells) following CD180 targeting. Unlike CD180 targeting, CD40 targeting only induced DCs but not B cells to become APCs and thus failed to efficiently induce T cell maturation, resulting in slower and lower-affinity IgG Ab responses. CD180 targeting induces a unique program in Ag-specific B cells and to our knowledge, is a novel strategy to induce Ag presentation in both DCs and B cells, especially immature B cells and thus has the potential to produce a broad range of Ab specificities. This study highlights the ability of immature B cells to present Ag to and induce the maturation of cognate T cells, providing insights toward vaccination of mature B cell-deficient individuals and implications in treating autoimmune disorders.
靶向 CD180 受体可激活 B 细胞和树突状细胞 (DC) 成为有效的 APC。将与抗 CD180 Ab 偶联的 Ag 接种到小鼠中后，B 细胞受体迅速被内化。值得注意的是，所有 B 细胞亚群，包括甚至过渡 1 B 细胞，都被编程为加工、呈递 Ag 并刺激 Ag 特异性 CD4 T 细胞。在 24-48 小时内，Ag 特异性 B 细胞可在脾脏的 T-B 边界处检测到；在那里，它们以依赖 T 细胞的方式增殖，并诱导 T 滤泡辅助 (Tfh) 细胞的成熟。值得注意的是，在 CD180 靶向后，未成熟 B 细胞足以使 T 细胞成熟：在 BAFFR 小鼠（仅具有过渡 1 B 细胞）而非 μMT 小鼠（缺乏所有 B 细胞）中诱导 T 细胞后，进行 CD180 靶向。与 CD180 靶向不同，CD40 靶向仅诱导 DC 而不是 B 细胞成为 APC，因此不能有效地诱导 T 细胞成熟，导致 IgG Ab 反应速度较慢且亲和力较低。CD180 靶向在 Ag 特异性 B 细胞中诱导了一个独特的程序，据我们所知，这是一种在 DC 和 B 细胞中诱导 Ag 呈递的新策略，特别是未成熟 B 细胞，因此具有产生广泛的 Ab 特异性的潜力。这项研究强调了未成熟 B 细胞向同源 T 细胞呈递 Ag 并诱导其成熟的能力，为成熟 B 细胞缺陷个体的疫苗接种提供了新的见解，并对治疗自身免疫性疾病具有重要意义。
