Role of Beclin-1 for the induction of autophagy in B lymphocytes

自噬是一种分解代谢过程，在此过程中，部分细胞质被双膜囊泡隔离并传递给溶酶体。在过去的十年中，对这一降解过程的分子理解得到了极大的促进，目前自噬在包括癌症、神经退行性疾病或传染病在内的致病性事件中的作用已被破译。B淋巴细胞是适应性免疫的核心组成部分，产生可溶性免疫球蛋白是已分化为浆细胞的B淋巴细胞的主要效应功能。在B淋巴细胞中，自噬在发育和MHC ii类依赖抗原呈递过程中都起着重要作用。在B淋巴细胞中，自噬似乎是由凋亡的B细胞抗原受体信号特异性诱导的。通常，诱导自噬的第一步是PI3K III类的激活。这种激活反过来依赖于包括Beclin-1/Atg6在内的多蛋白复合物。本项目的目的是分析Beclin-1在诱导B淋巴细胞自噬过程中的作用。这一发现将有助于更好地理解调节B细胞稳态的机制，从而对体液免疫反应产生重大影响。

Autophagy is a catabolic process during which portions of the cytoplasm are sequestered by double-membraned vesicles and delivered to lysosomes. During the past decade the molecular understanding of this degradative process has been promoted enormously, and currently the role of autophagy in pathogenic events including cancer, neurodegeneration, or infectious diseases is deciphered. B lymphocytes are a central component of adaptive immunity, and the production of soluble immunoglobulins represents the main effector function of B lymphocytes which have been differentiated to plasma cells. In B lymphocytes, autophagy plays an important role during both development and MHC class II-dependent antigen presentation. It seems that in B lymphocytes, autophagy is induced specifically by apoptotic B cell antigen receptor signaling. Generally, one initial step during the induction of autophagy is the activation of PI3K class III. This activation in turn depends on a multi-protein complex including Beclin-1/Atg6. The aim of the described project is to analyze the role of Beclin-1 during the induction of autophagy in B lymphocytes. The findings should then lead to a better understanding of the mechanisms regulating B cell homeostasis and thereby critically influencing the humoral immune response.