Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Immunol. 2010 Jan 1;184(1):442-51. doi: 10.4049/jimmunol.0900870. Epub 2009 Nov 30.
The pathogenic connection of type I IFN and its role in regulating the migration response of Ag delivery by B cells into lymphoid follicles in an autoimmune condition has not been well-identified. Here, we show that there was a significantly larger population of marginal zone precursor (MZ-P) B cells, defined as being IgM(hi)CD1d(hi)CD21(hi)CD23(hi) in the spleens of autoimmune BXD2 mice compared with B6 mice. MZ-P B cells were highly proliferative compared with marginal zone (MZ) and follicular (FO) B cells. The intrafollicular accumulation of MZ-P B cells in proximity to germinal centers (GCs) in BXD2 mice facilitated rapid Ag delivery to the GC area, whereas Ag-carrying MZ B cells, residing predominantly in the periphery, had a lower ability to carry Ag into the GCs. IFN-alpha, generated by plasmacytoid dendritic cells, induced the expression of CD69 and suppressed the sphingosine-1-phosphate-induced chemotactic response, promoting FO-oriented Ag transport by MZ-P B cells. Knockout of type I IFN receptor in BXD2 (BXD2-Ifnalphar(-/-)) mice substantially diffused the intrafollicular MZ-P B cell conglomeration and shifted their location to the FO-MZ border near the marginal sinus, making Ag delivery to the FO interior less efficient. The development of spontaneous GCs was decreased in BXD2-Ifnalphar(-/-) mice. Together, our results suggest that the MZ-P B cells are major Ag-delivery B cells and that the FO entry of these B cells is highly regulated by type I IFN-producing plasmacytoid dendritic cells in the marginal sinus in the spleens of autoimmune BXD2 mice.
I 型干扰素的致病联系及其在调节 B 细胞在自身免疫条件下向淋巴滤泡输送 Ag 的迁移反应中的作用尚未得到很好的确定。在这里，我们表明，与 B6 小鼠相比，自身免疫性 BXD2 小鼠脾脏中存在明显更多的边缘区前体 (MZ-P) B 细胞，其特征为 IgM(hi)CD1d(hi)CD21(hi)CD23(hi)。与边缘区 (MZ) 和滤泡 (FO) B 细胞相比，MZ-P B 细胞具有更高的增殖能力。BXD2 小鼠中 MZ-P B 细胞在生发中心 (GC) 附近的滤泡内积累，促进了 Ag 快速输送到 GC 区，而主要位于外周的带 Ag 的 MZ B 细胞将 Ag 带入 GC 的能力较低。浆细胞样树突状细胞产生的 IFN-α诱导 CD69 的表达，并抑制鞘氨醇-1-磷酸诱导的趋化反应，促进 MZ-P B 细胞向 FO 定向的 Ag 转运。在 BXD2（BXD2-Ifnalphar(-/-)）小鼠中敲除 I 型 IFN 受体，大大扩散了滤泡内 MZ-P B 细胞聚集体，并将其位置转移到边缘窦附近的 FO-MZ 边界，使 Ag 向 FO 内部的输送效率降低。BXD2-Ifnalphar(-/-) 小鼠中自发 GC 的发育减少。总之，我们的结果表明，MZ-P B 细胞是主要的 Ag 输送 B 细胞，这些 B 细胞进入 FO 的过程在很大程度上受到脾脏边缘窦中产生 I 型 IFN 的浆细胞样树突状细胞的调节。
