Anania Jessica C, Westin Annika, Adler Jeremy, Heyman Birgitta
Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Facilities, BioVis, Uppsala University, Uppsala, Sweden.
Front Immunol. 2021 Apr 12;12:655753. doi: 10.3389/fimmu.2021.655753. eCollection 2021.
Follicular dendritic cells (FDCs) are rare and enigmatic cells that mainly reside in germinal centers (GCs). They are capable of capturing immune complexes, their Fc (FcRs) and complement receptors (CRs) and storing them for long periods in non-degradative vesicles. Presentation of ICs on FDCs to B cells is believed to drive affinity maturation. CR1 and CR2 are expressed on B cells and FDCs. Cr2 knock out (KO) mice, lacking both receptors, have impaired antibody and GC responses. Utilizing a novel ImageJ macro to analyze confocal fluorescence microscopy images of spleen sections, we here investigate how FDCs in wild type (WT) and Cr2 KO mice behave during the first two weeks after immunization with sheep red blood cells (SRBC). Mice were immunized with SRBC i.v. and spleen and serum samples harvested at various time points. As expected, antibody and GC responses in Cr2 KO mice were impaired in comparison to WT mice. Fewer FDCs were identified in Cr2 KO mice, and these exhibited differential localization and organization in comparison to WT mice. WT FDCs were primarily located within GCs at the light zone/dark zone border. FDCs from WT but not Cr2 KO mice were actively dispersed in GCs, i.e. tended to move away from each other, presumably to increase their surface area for B cell interaction. FDCs from Cr2 KO mice were more often found on follicles outside of the GCs and those within the GCs were closer to the periphery in comparison to WT FDCs. Expression of CR1 and CR2, FcγRIIB, and FcµR increased in FDCs from WT mice during the course of immunization. The results suggest that decreased ability to capture ICs by FDCs lacking CR1 and CR2 may not be the only explanation for the impaired GC and antibody responses in Cr2 KO mice. Poor FDC organization in GCs and failure to increase receptor expression after immunization may further contribute to the inefficient immune responses observed.
滤泡树突状细胞（FDCs）是一类罕见且神秘的细胞，主要存在于生发中心（GCs）。它们能够捕获免疫复合物、其Fc（FcRs）和补体受体（CRs），并将它们长时间储存在非降解性囊泡中。FDCs上的免疫复合物向B细胞的呈递被认为会驱动亲和力成熟。CR1和CR2在B细胞和FDCs上表达。Cr2基因敲除（KO）小鼠由于缺乏这两种受体，其抗体和GC反应受损。利用一种新颖的ImageJ宏程序来分析脾脏切片的共聚焦荧光显微镜图像，我们在此研究野生型（WT）和Cr2 KO小鼠的FDCs在用绵羊红细胞（SRBC）免疫后的前两周内的行为表现。小鼠经静脉注射SRBC进行免疫，并在不同时间点采集脾脏和血清样本。正如预期的那样，与WT小鼠相比，Cr2 KO小鼠的抗体和GC反应受损。在Cr2 KO小鼠中鉴定出的FDCs较少，并且与WT小鼠相比，它们表现出不同的定位和组织方式。WT FDCs主要位于生发中心的明区/暗区边界内。来自WT而非Cr2 KO小鼠的FDCs在生发中心内呈活跃分散状态，即倾向于相互远离，推测这是为了增加其与B细胞相互作用的表面积。与WT FDCs相比，来自Cr2 KO小鼠的FDCs更常出现在生发中心外的滤泡上，而生发中心内的那些FDCs则更靠近周边。在免疫过程中，WT小鼠FDCs中CR1和CR2、FcγRIIB以及FcµR的表达增加。结果表明，缺乏CR1和CR2的FDCs捕获免疫复合物能力的下降可能不是Cr2 KO小鼠生发中心和抗体反应受损的唯一解释。生发中心内FDCs组织不良以及免疫后未能增加受体表达可能进一步导致了所观察到的低效免疫反应。
