Very early plasma cell differentiation

摘要 激活的B细胞启动抗体合成的生化途径 同时进行细胞分裂时的细胞和分泌物是未知的。当前 模型预测早期的浆细胞产生所需的细胞器结构 通过激活未折叠蛋白反应(UPR)来促进抗体的分泌 以增加抗体合成，并通过有丝分裂依赖的过程。这个项目 中心放在另一种模型上，激活的B细胞为浆细胞功能做准备 通过在增加抗体合成之前很久就制定了UPR，并独立于 有丝分裂。因此，我们认为在B细胞中诱导UPR是同样主动的 是被动的。我们将测试这一新模型，同时还将剖析过去观察到的 边缘带B细胞产生浆细胞的速度比大多数B细胞快得多。我们建议 三个具体目标：1)确定协调早期PC的生化途径 分化，2)确定结构性mTORC1信号在MZ B细胞中的作用 (3)有丝分裂与早期PC分化分离。

Abstract The biochemical pathways through which activated B cells initiate antibody synthesis and secretion while simultaneously undergoing cell division are unknown. Current models predict that early plasma cells generate the organelle structures needed for robust antibody secretion by activating the unfolded protein response (UPR) in response to increased antibody synthesis and through a mitosis-dependent process. This project centers on an alternative model where activated B cells prepare for plasma cell function by enacting the UPR well before increased antibody synthesis and independently of mitosis. Hence we propose that induction of the UPR in B cells is as much proactive as it is reactive. We will test this new model while also dissecting the past observations that marginal zone B cells generate plasma cells much faster than most B cells. We propose three specific aims: 1) Define biochemical pathways coordinating very early PC differentiation, 2) Define the role of constitutive mTORC1 signaling in MZ B cell differentiation, and 3) Uncouple mitosis and early PC differentiation.