Reelin对B细胞在骨髓内发育和迁移的影响研究

前期工作中，我们发现调节神经元迁移和层状排列、稳定细胞骨架的关键分子reelin在pre-B和immature B细胞特异性高表达。与野生型相比，Reelin天然缺陷鼠骨髓中pre-B和immature B细胞数少，体外存活能力减弱。我们推测reelin可能通过促进骨髓内B细胞亚群的存活和不同龛位间的迁移来辅助调控B细胞发育。本项目将通过以下几方面的研究验证这一推测：1）利用基因突变鼠和骨髓重建等模型分析reelin缺陷和过表达对B细胞在骨髓内外的分布、B细胞亚群的存活、增殖、分化和迁移的影响；2）探讨reelin调节B细胞行为的分子机理；3）探讨reelin在B细胞中的表达调控。研究结果将有助于深入理解B细胞的分化和迁移机理以及骨髓微环境对这些过程的影响，并有望为reelin表达异常以及其它病理情况或治疗后的免疫功能恢复提供医学干预的新思路。

Reelin is an extracellular matrix glycoprotein that plays a pivotal role in the regulation of cell migration and positioning control. Little is known of the role of reelin on lymphocyte development. We found high expression of reelin in pre-B and immature B cells in the bone marrow. Mice with natural deficiency in reelin had less pre-B and immature B cells. Compared to those from wild type, the reelin-deficient B cell populations undergo more apoptosis in vitro. Thus, we hypothesize that reelin may play an important role in promoting the survival and niche-to-niche migration of developing B cells in the bone marrow. We will use mouse models with loss-of-function and gain-of-function of reelin to study B cell migration and development in the bone marrow. The molecular mechanism of reelin in regulating B cell behavior will be also investigated. We will also explore the regulation of reelin expression in B cells. The results from this research will facilitate our understanding of B cell development/migration and the role of the bone marrow microenvironment on B cells. This study may also provide novel therapeutic approach to alleviate immune functions in patients with reelin defects or after the treatment of immune ablation.