MUrine Tools to Catch High Affinity Plasma cells (MUTCHAP)

免疫球蛋白亲和成熟发生在生发中心(GC)。我们最近描述了接种疫苗后特定时间从GC中涌出的浆细胞群(Meyer-Hermann等人，Cell Rep，2012)。然而，目前还没有已知的标记专门识别这一群体。我们计划使用小鼠的基因工程来鉴定GC来源的浆母细胞，以诱导荧光蛋白在浆细胞生成过程中被激活。这应该会导致一种新的小鼠模型，它可以识别免疫或感染后最近进入浆细胞分化的GC细胞。这些小鼠可以作为模型来研究生发中心的浆细胞分化，它们在活组织中的迁移，或者帮助分离它们，以便在单细胞水平上研究基因和蛋白质的表达。这个项目将检验这样的假设，即这些浆细胞是产生长期高亲和力抗体反应的关键成分。此外，我们将测试哪些信号正在调节它们的外观。这也可能导致产生更有效的单抗药物的新方法。

Immunoglobulin affinity maturation happens in the germinal centre (GC). We recently described a population of plasma cells emerging from GCs at specific times after vaccination (Meyer-Hermann et al., Cell Rep, 2012). However, there are currently no known markers specifically identifying this population. We plan to identify GC derived plasmablasts using genetic engineering of mice to induce fluorescent proteins being activated during plasma cell generation. This should lead to a novel mouse model which can identify GC cells that recently entered plasma cell differentiation, following immunisation or infection. The mice can be used as models to study plasma cell differentiation from the germinal centre, their migration in live tissues using intravital light sheet microscopy, or aid their isolation so that gene and protein expression can be studied on single cell level.This project will test the hypothesis that these plasma cells are key components producing long term high affinity antibody responses. Further, we will test which signals are regulating their appearance. This may also lead to new ways of generating more efficiently monoclonal antibody drugs.