Molecular Analyses of the individual function of the transcriptional Co-Activator BOB.1/OBF.1 in B versus T lymphocytes and its specific contribution to the Germinal Center Reaction

BOB.1 /票据。1最初被描述为B细胞特异性转录共激活因子。BOB.1 /票据。1本身对DNA只有非常弱的亲和力，但被转录因子Oct1和Oct2招募到所谓的Octamer基序，从而增强了Octamer依赖性转录。BOB.1 /票据。1缺陷小鼠在B细胞发育的不同阶段表现出严重缺陷，但在某些T细胞群，如TH1、TH2或滤泡T辅助细胞（TFH）中也表现出严重缺陷。1/OBF的主要特点。1缺陷小鼠完全没有生发中心，因此也没有生发中心衍生的B细胞，如血浆和记忆B细胞。然而，生发中心的缺乏是否完全是由BOB.1/OBF引起的，这个问题尚不完全清楚。B细胞中1的缺乏，或者如果加上低效的T细胞帮助，特别是由TFH提供，也有助于这种严重的表型。由于缺乏适当的工具来调节BOB.1/OBF。到目前为止，我们还不能确定BOB.1/OBF在这些终末细胞分化阶段的确切影响。1到生发中心反应通过精确的分子分析。此外，研究BOB.1/OBF的选择也很有限。在存在野生型B细胞的情况下T细胞中缺乏1，反之亦然。我们现在已经生成了带有floxed BOB.1/OBF的小鼠。1等位基因。这样的鼠标系统允许有条件地删除BOB.1/OBF。因此，在缺乏转录共激活因子的情况下，可以精确分析B细胞和t细胞的分化和功能。利用我们的条件系统和合适的表达Cre的小鼠系，我们现在能够分析BOB.1/OBF的具体需求。1在b细胞发育早期和晚期的表达以及BOB.1/OBF的需求。1对特定T细胞亚群的功能。我们项目的一个主要焦点是对BOB.1/OBF的识别和进一步表征。1个靶基因，以了解BOB.1/OBF的影响。生理条件下b细胞的发育和功能。此外，这些分析使我们能够理解BOB.1/OBF如何。如果它在定义的B细胞和T细胞亚群中完全缺失，则会影响生发中心反应。此外，由于我们新生成的系统，我们现在能够表征BOB.1/OBF的个体相关性。从而进一步阐明BOB.1/OBF在免疫病理条件下的作用。在自身免疫过程中因此，本文提出的研究的目的是鉴定转录共激活子BOB.1/OBF的分子机制。1参与了B细胞和T细胞的发育和分化，也参与了BOB.1/OBF的新功能。在生理和免疫病理条件下的这些过程中。

BOB.1/OBF.1 was originally described as a B cell specific transcriptional co-activator. BOB.1/OBF.1 itself has only very weak affinity to DNA but is recruited by the transcription factors Oct1 and Oct2 to the so called Octamer motif and thereby enhances Octamer-dependent transcription. BOB.1/OBF.1-deficient mice show severe defects at different stages of B cell development, but also in certain T cell populations, like TH1, TH2 or follicular T-helper cells (TFH). The main characteristic of BOB.1/OBF.1-deficient mice is the complete absence of germinal centers and consequently also of germinal center derived B cells, like plasma and memory B cells. However, the question is not fully understood, whether the lack of germinal centers is caused exclusively by the BOB.1/OBF.1 deficiency in B cells or if in addition an inefficient T cell help, provided particularly by TFH, also contributes to this severe phenotype. Because of the lack of appropriate tools to regulate BOB.1/OBF.1 expression in these terminal cell differentiation stages so far we were not able to define the exact impact of BOB.1/OBF.1 to the germinal center reaction by precise molecular analyses. Furthermore, there were only limited options to study BOB.1/OBF.1 deficiency in T cells in the presence of wildtype B cells and vice versa.We have now generated mice bearing floxed BOB.1/OBF.1 alleles. Such a mouse system allows the conditional deletion of BOB.1/OBF.1 expression and therefore the precise analyses of B- as well as T-cell differentiation and function in the absence of the transcriptional co-activator. Using our conditional system together with appropriate Cre expressing mouse lines we are now able to analyze the specific need of BOB.1/OBF.1 expression in early and also in late stages of B-cell development as well as the requirement of BOB.1/OBF.1 for the function of specific T cell subpopulations. A main focus of our project is the identification and further characterization of BOB.1/OBF.1 target genes in order to understand the influence of BOB.1/OBF.1 on B-cell development and function under physiological conditions. Moreover, these analyses allow us to understand how BOB.1/OBF.1 affects germinal center reaction if it is exclusively deleted in defined B and T cell subpopulations. Additionally, due to our newly generated system we are now able to characterize the individual relevance of BOB.1/OBF.1 under immune-pathological conditions and thus to further elucidate the role of BOB.1/OBF.1 in autoimmune processes. Therefore, the aim of the here proposed study is the identification of molecular mechanisms in which the transcriptional co-activator BOB.1/OBF.1 is involved during B and T cell development and differentiation as well as new functions of BOB.1/OBF.1 in those processes under physiological and also immune-pathological conditions.