Nonhematopoietic stromal cells in lymph nodes such as fibroblastic reticular cells (FRCs) can support the survival of plasmablasts and plasma cells [together, antibody-forming cells (AFCs)]. However, a regulatory function for the stromal compartment in AFC accumulation has not been appreciated. Here, we show that chemokine ligand 2 (CCL2)–expressing stromal cells limit AFC survival. FRCs express high levels of CCL2 in vessel-rich areas of the T cell zone and the medulla, where AFCs are located. FRC CCL2 is up-regulated during AFC accumulation, and we use lymph node transplantation to show that CCL2 deficiency in BP3⁺ FRCs and lymphatic endothelial cells increases AFC survival without affecting B or germinal center cell numbers. Monocytes are key expressers of the CCL2 receptor CCR2, as monocyte depletion and transfer late in AFC responses increases and decreases AFC accumulation, respectively. Monocytes express reactive oxygen species (ROS) in an NADPH oxidase 2 (NOX2)–dependent manner, and NOX2-deficient monocytes fail to reduce AFC numbers. Stromal CCL2 modulates both monocyte accumulation and ROS production, and is regulated, in part, by manipulations that modulate vascular permeability. Together, our results reveal that the lymph node stromal compartment, by influencing monocyte accumulation and functional phenotype, has a regulatory role in AFC survival. Our results further suggest a role for inflammation-induced vascular activity in tuning the lymph node microenvironment. The understanding of stromal-mediated AFC regulation in vessel-rich environments could potentially be harnessed to control antibody-mediated autoimmunity.

淋巴结中的非造血基质细胞，例如成纤维细胞网状细胞（FRC）可以支持成浆细胞和浆细胞[一起，抗体形成细胞（AFC）]的生存。但是，尚未认识到AFC积累中基质室的调节功能。在这里，我们表明趋化因子配体2（CCL2）表达基质细胞限制AFC生存。FRC在AFC所在的T细胞区和髓质的血管丰富区域表达高水平的CCL2。FRC CCL2在AFC积累过程中被上调，我们使用淋巴结移植来显示BP3 ⁺中CCL2缺乏FRC和淋巴管内皮细胞可提高AFC存活率，而不会影响B或生发中心细胞数量。单核细胞是CCL2受体CCR2的关键表达，因为单核细胞的耗竭和AFC响应后期的转移分别增加和减少了AFC的积累。单核细胞以NADPH氧化酶2（NOX2）依赖的方式表达活性氧（ROS），而缺乏NOX2的单核细胞无法减少AFC数量。基质CCL2调节单核细胞积累和ROS生成，并部分受到调节血管通透性的操纵的调节。总之，我们的结果表明，淋巴结基质区室通过影响单核细胞的积累和功能表型，对AFC的存活具有调节作用。我们的结果进一步表明炎症诱导的血管活性在调节淋巴结微环境中具有作用。在血管丰富的环境中对基质介导的AFC调控的理解可能可以用来控制抗体介导的自身免疫。