Immunobiology and Cancer Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Mol Immunol. 2011 Oct;49(1-2):367-79. doi: 10.1016/j.molimm.2011.09.008. Epub 2011 Oct 2.
Previous data suggested that constitutive expression of the transcription factor Bright (B cell regulator of immunoglobulin heavy chain transcription), normally tightly regulated during B cell differentiation, was associated with autoantibody production. Here we show that constitutive Bright expression results in skewing of mature B lineage subpopulations toward marginal zone cells at the expense of the follicular subpopulation. C57Bl/6 transgenic mice constitutively expressing Bright in B lineage cells generated autoantibodies that were not the result of global increases in immunoglobulin or of breaches in key tolerance checkpoints typically defective in other autoimmune mouse models. Rather, autoimmunity correlated with increased numbers of marginal zone B cells and alterations in the phenotype and gene expression profiles of lymphocytes within the follicular B cell compartment. These data suggest a novel role for Bright in the normal development of mature B cell subsets and in autoantibody production.
先前的数据表明,转录因子 Bright(免疫球蛋白重链转录的 B 细胞调节因子)的组成型表达与自身抗体的产生有关,而在 B 细胞分化过程中,Bright 的表达通常受到严格调控。在这里,我们发现组成型表达 Bright 会导致成熟 B 细胞亚群向边缘区细胞倾斜,而滤泡亚群减少。在 B 细胞中组成型表达 Bright 的 C57Bl/6 转基因小鼠产生了自身抗体,但这不是由于免疫球蛋白的全面增加,也不是由于其他自身免疫性小鼠模型中通常存在缺陷的关键耐受检查点的破裂所致。相反,自身免疫与边缘区 B 细胞数量的增加以及滤泡 B 细胞区室中淋巴细胞表型和基因表达谱的改变相关。这些数据表明 Bright 在成熟 B 细胞亚群的正常发育和自身抗体产生中具有新的作用。