Lindhout E, Vissers J L, Hartgers F C, Huijbens R J, Scharenborg N M, Figdor C G, Adema G J
Department of Tumor Immunology, University Medical Center, Nijmegen, The Netherlands.
J Immunol. 2001 Mar 1;166(5):3284-9. doi: 10.4049/jimmunol.166.5.3284.
DC-CK1 (CCL18) is a dendritic cell (DC)-specific chemokine expressed in both T and B cell areas of secondary lymphoid organs that preferentially attracts CD45RA(+) T cells. In this study, we further explored the nature of DC-CK1 expressing cells in germinal centers (GCs) of secondary lymphoid organs using a newly developed anti-DC-CK1 mAb. Immunohistochemical analysis demonstrated a remarkable difference in the number of DC-CK1 expressing cells in adjacent GCs within one tonsil, implicating that the expression of DC-CK1 in GCs depends on the activation and/or progression stage of the GC reaction. Using immunohistology and RNA analysis, we demonstrated that GCDC are the source of DC-CK1 production in the GCs. Considering the recently described function of GCDC in (naive) B cell proliferation, isotype switching and Ab production, we investigated the ability of DC-CK1 to attract B lymphocytes. Here we demonstrate that DC-CK1 is a pertussis toxin-dependent chemoattractant for B lymphocytes with a preference in attracting mantle zone (CD38(-)) B cells. The findings that GCDC produce DC-CK1 and attract mantle zone B cells support a key role for GCDC in the development of GCs and memory B cell formation.
DC-CK1(CCL18)是一种树突状细胞(DC)特异性趋化因子,在次级淋巴器官的T细胞和B细胞区域均有表达,优先吸引CD45RA(+) T细胞。在本研究中,我们使用新开发的抗DC-CK1单克隆抗体,进一步探究了次级淋巴器官生发中心(GC)中表达DC-CK1的细胞的性质。免疫组织化学分析显示,在一个扁桃体的相邻生发中心中,表达DC-CK1的细胞数量存在显著差异,这表明生发中心中DC-CK1的表达取决于生发中心反应的激活和/或进展阶段。通过免疫组织学和RNA分析,我们证明生发中心暗区细胞(GCDC)是生发中心中DC-CK1的产生来源。考虑到最近描述的GCDC在(幼稚)B细胞增殖、同种型转换和抗体产生中的功能,我们研究了DC-CK1吸引B淋巴细胞的能力。在此我们证明,DC-CK1是一种依赖百日咳毒素的B淋巴细胞趋化因子,优先吸引套区(CD38(-))B细胞。GCDC产生DC-CK1并吸引套区B细胞的发现,支持了GCDC在生发中心发育和记忆B细胞形成中的关键作用。