Role of BAFF in regulation of B cell peripheral tolerance

描述（由申请方提供）：在抗原驱动的B细胞应答期间产生的自身反应性B细胞负调控的潜在机制仍然不清楚。本奖学金申请中描述的项目集中于了解细胞因子BAFF在调节DNA反应性B细胞进入生殖中心B细胞反应中的作用。通过使用独特的转基因小鼠品系，将确定BAFF对自身反应性B细胞命运的影响。具体目标是：1）确定滤泡辅助T细胞的BAFF表达是否改变了自身反应性生发中心B细胞的反选择;和2）确定生发中心B细胞TACI受体表达的变化是否干扰了自身反应性生发中心B细胞的反选择。这些研究将提供有关自身反应性B细胞调节的基本信息，这些细胞是包括狼疮在内的各种自身免疫性疾病中致病抗体的来源，因此将完成NIHLB输血医学和细胞治疗学项目的使命。

DESCRIPTION (provided by applicant): The mechanisms underlying the negative regulation of self-reactive B cells that arise during antigen-driven B cell responses remain obscure. The project described in this fellowship application centers on understanding the role of the cytokine BAFF in the regulation of DNA-reactive B cells that enter the germinal center B cell response. Through the use of unique transgenic mouse lines, the influence of BAFF on the fate of self-reactive B cells will be determined. The specific aims are: 1) determine whether BAFF expression by follicular helper T cells alters counter-selection of self-reactive germinal center B cells; and 2) determine whether changes in germinal center B cell TACI receptor expression disturb the counter-selection of self-reactive germinal center B cells. These studies will provide fundamental information on the regulation of self-reactive B cells, which are the source of pathogenic antibodies in a variety of autoimmune disorders including Lupus, and will therefore fulfill the mission of the Transfusion Medicine and Cellular Therapeutics program of the NIHLB.