Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J Immunol. 2013 May 1;190(9):4465-9. doi: 10.4049/jimmunol.1300041. Epub 2013 Mar 29.
Marginal zone macrophages (MZMs) act as a barrier to entry of circulating apoptotic debris into the follicles of secondary lymphoid organs. In autoimmune BXD2 mice, there is a progressive reduction in the function and numbers of MZMs. Absence of MZMs results in retention of apoptotic cell (AC) debris within the marginal zone (MZ) and increased loading of AC Ags on MZ B cells and MZ-precursor (MZ-P) B cells. The MZ-P B cells are capable of translocating the AC Ags to the follicular zone and stimulating T cells. Both MZMs and MZ-P B cells from BXD2 mice express low levels of tolerogenic signals and high levels of inflammatory signals. Thus, the current study suggests a multifaceted mechanism in which MZMs maintain tolerance to apoptotic autoantigens and suppress their translocation to follicles. Lack of clearance of apoptotic debris by MZMs drives follicular Ag-transportation by MZ-P B cells to stimulate an autoimmune response.
边缘区巨噬细胞 (MZMs) 作为阻止循环凋亡细胞进入次级淋巴器官滤泡的屏障。在自身免疫性 BXD2 小鼠中，MZMs 的功能和数量逐渐减少。MZMs 的缺失导致凋亡细胞 (AC) 碎片在边缘区 (MZ) 中滞留，并增加了 AC Ag 在 MZ B 细胞和 MZ 前体 (MZ-P) B 细胞上的负载。MZ-P B 细胞能够将 AC Ag 易位到滤泡区并刺激 T 细胞。来自 BXD2 小鼠的 MZMs 和 MZ-P B 细胞均表达低水平的耐受信号和高水平的炎症信号。因此，目前的研究表明，MZMs 通过多种机制维持对凋亡自身抗原的耐受，并抑制其向滤泡的易位。MZMs 对凋亡细胞碎片的清除不足，促使 MZ-P B 细胞进行滤泡 Ag 转运，从而刺激自身免疫反应。
