记忆B细胞异质性与其命运决定的研究

Memory B cell (MBC) is commonly defined as antigen-experienced, resting B cells which could quickly response to the secondary stimulation, essential for immune memory defense in humoral immunity besides antibody and long-lived plasma cells. MBC mainly derived from germinal center (GC), and undergo multiple somatic mutation, selection. However, lots remain unclear in MBC formation, maintenance and its function in secondary response. Our group come up the hypothesis “Store-Recycle Model” combining previous work from other groups and our work published, screening unique location or signaling features of MBC after formation and trying to describe the resting stage of MBC in primary response. Besides, by taking advantage of BLIBA, the ratio of two transcriptional factors Blimp-1 and Bach2, we could predict the direction of the fate determination of MBC during its re-differentiation. It is called the “Intrinsic Determination Model”, in which the MBC with higher BLIBA tend to differentiate into PC while MBC with lower BLIBA prefer to become GC during re-stimulation. We will search the critical factors for MBC location, maintenance and function by utilizing our newly designed MBC tracing mice, and change BLIBA of MBC in vivo spatio-temporally during secondary response through inducible expression system we built. Overall, our group trying to make a step further in understanding the nature of MBC maintenance and differentiation in a distinct aspect.

记忆B细胞（MBC）是经历过抗原的静息B细胞，在二次应答时快速产生生发中心B细胞（GC B）与浆细胞（PC）。MBC主要产生于GC，但关于MBC如何产生、维持、二次应答尚不明确。结合前人研究与本人已发表成果，研究组提出“存储-再循环“模型，寻找记忆B细胞在形成后的定位与信号特征，以解释记忆B细胞在初次免疫应答中处于静息态这一特质。针对记忆B细胞再分化过程中的命运决定，研究组提出了” 内因决定模型“，利用两个转录因子Blimp1与BACH2表达量比BLIBA，判断记忆B细胞的分化方向：比例更高更倾向于形成浆细胞，而比例更低更倾向于形成生发中心B细胞。研究组拟采用全新的记忆B细胞示踪鼠寻找记忆B细胞体内定位，维持与功能的核心要素，并利用可诱导表达系统在体内定向改变已形成的记忆B细胞的BLIBA，观测其二次免疫应答中的分化情况。综上，研究组试图以全新思考角度，探究记忆B细胞维持与分化的本质。

记忆B细胞（MBC）是经历过抗原的静息B细胞，在二次应答时快速产生生发中心B细胞（GC B）与浆细胞（PC）。MBC主要产生于GC，但关于MBC如何产生、维持、二次应答尚不明确。结合前人研究与本人已发表成果，研究组提出“存储-再循环“模型，寻找记忆B细胞在形成后的定位与信号特征，以解释记忆B细胞在初次免疫应答中处于静息态这一特质。针对记忆B细胞再分化过程中的命运决定，研究组提出了” 内因决定模型“，利用两个转录因子Blimp1与BACH2表达量比BLIBA，判断记忆B细胞的分化方向：比例更高更倾向于形成浆细胞，而比例更低更倾向于形成生发中心B细胞。研究组拟采用全新的记忆B细胞示踪鼠寻找记忆B细胞体内定位，维持与功能的核心要素，并利用可诱导表达系统在体内定向改变已形成的记忆B细胞的BLIBA，观测其二次免疫应答中的分化情况。综上，研究组试图以全新思考角度，探究记忆B细胞维持与分化的本质。