Dogusan Zeynep, Montecino-Rodriguez Encarnacion, Dorshkind Kenneth
Department of Pathology and Laboratory Medicine and the Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
J Immunol. 2004 Apr 15;172(8):4717-23. doi: 10.4049/jimmunol.172.8.4717.
It has been hypothesized that B cell precursors that undergo programmed cell death due to nonproductive Ig gene rearrangements are cleared from the bone marrow by macrophages. However, a role for macrophages in this process is supported only by micrographs showing their association with apoptotic-appearing, B lineage cells. Functional data demonstrating phagocytosis of apoptotic, bone marrow lymphocytes by macrophages have not been presented, nor have receptors potentially involved in that process been identified. The data in this report demonstrate that macrophages isolated from murine bone marrow efficiently phagocytose apoptotic murine B lineage cells using multiple receptors that include CD14, integrins, class A scavenger receptor, and CD31 (PECAM-1). In addition, the results further reveal a new role for the hemopoietic microenvironment in B cell development in view of data demonstrating that murine bone marrow stromal cells are also capable of clearing apoptotic cells via an integrin-dependent mechanism.
有假说认为,由于免疫球蛋白(Ig)基因重排无效而经历程序性细胞死亡的B细胞前体,会被巨噬细胞从骨髓中清除。然而,巨噬细胞在此过程中的作用仅得到显微照片的支持,这些照片显示它们与呈现凋亡状态的B谱系细胞有关联。尚未提供功能性数据证明巨噬细胞对凋亡的骨髓淋巴细胞进行吞噬作用,也未鉴定出可能参与该过程的受体。本报告中的数据表明,从小鼠骨髓中分离出的巨噬细胞利用包括CD14、整合素、A类清道夫受体和CD31(血小板内皮细胞黏附分子-1)在内的多种受体,有效地吞噬凋亡的小鼠B谱系细胞。此外,鉴于数据表明小鼠骨髓基质细胞也能够通过整合素依赖性机制清除凋亡细胞,这些结果进一步揭示了造血微环境在B细胞发育中的新作用。