Department of Medicine, Division of Clinical Immunology and Rheumatology, the University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA.
Clin Immunol. 2023 Dec;257:109842. doi: 10.1016/j.clim.2023.109842. Epub 2023 Nov 18.
Cardinal features of lupus include elevated B cell activation and autoantibody production with a female sex preponderance. We quantified interactions of sex and genetic variation on the development of autoimmune B-cell phenotypes and autoantibodies in the BXD2 murine model of lupus using a cohort of backcrossed progeny (BXD2 x C57BL/6J) x BXD2. Sex was the key factor leading to increased total IgG, IgG2b, and autoantibodies. The percentage of T-betCD11c IgD activated naive B cells (aNAV) was higher in females and was associated with increased T-betCD11c IgD age-related B cells, FasGL7 germinal center B cells, Cxcr5Icos peripheral T-helper cells, and Cxcr5Icos follicular T-helper cells. IFN-β was elevated in females. Variation in aNAV cells was mapped to Chr 7 in a locus that shows significant interactions between the female sex and heterozygous B/D variant. Our results suggest that activation of naive B cells forms the basis for the female-predominant development of autoantibodies in lupus-susceptible BXD2 mice.
狼疮的主要特征包括 B 细胞激活和自身抗体产生增加，且女性居多。我们使用狼疮 BXD2 小鼠模型的回交后代（BXD2 x C57BL/6J）x BXD2 队列，定量分析了性别和遗传变异对自身免疫性 B 细胞表型和自身抗体发展的影响。性别是导致总 IgG、IgG2b 和自身抗体增加的关键因素。T-betCD11c IgD 激活的幼稚 B 细胞（aNAV）在女性中比例更高，与 T-betCD11c IgD 年龄相关的 B 细胞、FasGL7 生发中心 B 细胞、Cxcr5Icos 外周辅助性 T 细胞和 Cxcr5Icos 滤泡辅助性 T 细胞的增加有关。女性 IFN-β 水平升高。aNAV 细胞的变异映射到 Chr 7 上的一个位点，该位点显示女性性别和杂合 B/D 变异之间存在显著的相互作用。我们的研究结果表明，幼稚 B 细胞的激活是狼疮易感 BXD2 小鼠中女性为主的自身抗体发展的基础。
