Williams Jesse W, Elvington Andrew, Kessler Skyler, Wohltmann Mary, Wu Gregory F, Randolph Gwendalyn J
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; and.
Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110.
Immunohorizons. 2019 Jan 21;3(1):37-44. doi: 10.4049/immunohorizons.1800015.
Depletion of B cells attenuates plaque development and modulates T cell responses in mouse models of atherosclerosis, suggesting that Ag presentation by B cells may promote disease progression. Thus, we set out to determine the role of B cell-mediated MHC class II (MHC II) Ag presentation during atherosclerotic plaque development. We developed murine conditional MHC II deletion and expression systems under control of the B cell-restricted CD19 promoter in an experimental model of atherosclerosis. Mice lacking MHC II expression only on B cells exhibited systemic shifts in germinal center and marginal zone B cell populations, leading to a reduced Ab response compared with littermate control animals. However, all populations were present and normal cholesterol uptake was detected in the plasma following high-fat diet treatment. In a second model, in which conditional expression of MHC II is limited only to B cells, showed similar overall cellularity characteristics compared with mice with complete MHC II deficiency. High-fat diet feeding showed no major changes in atherosclerotic plaque size or plaque cellular content in either conditional deletion or conditional expression approaches, compared with control animals. By testing the necessity and sufficiency of MHC II on B cells in the progression of atherosclerosis, we determine that MHC II on B cells does not directly regulate lesion development in murine models.
在动脉粥样硬化小鼠模型中，B细胞的缺失可减弱斑块形成并调节T细胞反应，这表明B细胞提呈抗原可能促进疾病进展。因此，我们着手确定B细胞介导的MHC II类（MHC II）抗原提呈在动脉粥样硬化斑块形成过程中的作用。在动脉粥样硬化实验模型中，我们构建了在B细胞限制性CD19启动子控制下的小鼠条件性MHC II缺失和表达系统。仅在B细胞上缺乏MHC II表达的小鼠，其生发中心和边缘区B细胞群体出现全身性改变，与同窝对照动物相比，抗体反应降低。然而，所有细胞群体均存在，高脂饮食处理后血浆中胆固醇摄取正常。在第二个模型中，MHC II的条件性表达仅限于B细胞，与完全缺乏MHC II的小鼠相比，其总体细胞特征相似。与对照动物相比，在条件性缺失或条件性表达方法中，高脂饮食喂养对动脉粥样硬化斑块大小或斑块细胞成分均无重大影响。通过检测B细胞上MHC II在动脉粥样硬化进展中的必要性和充分性，我们确定B细胞上的MHC II在小鼠模型中不直接调节病变发展。
