Dammers Peter M, Kroese Frans G M
Department of Cell Biology, Histology and Immunology Section, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands.
Eur J Immunol. 2005 Jul;35(7):2089-99. doi: 10.1002/eji.200526118.
Marginal zone B (MZ-B) cells of the spleen contribute significantly to the immunity against invasive infections with polysaccharide-encapsulated bacteria. Recent evidence indicates that recruitment and selection of MZ-B cells occurs on the basis of positive selection constraints that likely operate via B cell receptor (BCR) signaling. Previous studies have shown that MZ-B cells carry relatively shorter immunoglobulin (Ig) heavy (H) chain complementarity-determining region 3 (H-CDR3) sequences and express BCR which are thought to be polyreactive. In this scenario, MZ-B cell selection proceeds via engagement of the BCR with exogenous (i.e. microbial gut flora-derived) and/or endogenous (self) antigens. Here, we studied the influence of exogenous antigens on the selection process of MZ-B cells using non-genetically manipulated adult germ-free and conventionally reared infant rats. This study was carried out by H-CDR3 spectratype analysis of V(H)(PC7183)-encoded Ig V(H)DJ(H)-mu transcripts expressed by purified splenic MZ-B cells and other B cell subsets. We show that MZ-B cells in both adult germ-free and conventionally reared infant (14-day-old) rats are H-CDR3-selected cells, providing strong evidence that recruitment and selection of MZ-B cells is driven by self antigens.
脾脏的边缘区B(MZ-B)细胞对抵御多糖包膜细菌的侵袭性感染免疫有重要贡献。最近的证据表明,MZ-B细胞的募集和选择是基于可能通过B细胞受体(BCR)信号传导起作用的阳性选择限制。先前的研究表明,MZ-B细胞携带相对较短的免疫球蛋白(Ig)重链互补决定区3(H-CDR3)序列,并表达被认为具有多反应性的BCR。在这种情况下,MZ-B细胞的选择通过BCR与外源性(即微生物肠道菌群衍生的)和/或内源性(自身)抗原的结合来进行。在这里,我们使用未进行基因操作的成年无菌和常规饲养的幼鼠研究了外源性抗原对MZ-B细胞选择过程的影响。这项研究是通过对纯化的脾脏MZ-B细胞和其他B细胞亚群表达的V(H)(PC7183)编码的Ig V(H)DJ(H)-μ转录本进行H-CDR3谱型分析来进行的。我们表明,成年无菌和常规饲养的幼鼠(14日龄)中的MZ-B细胞都是H-CDR3选择的细胞,这提供了强有力的证据,证明MZ-B细胞的募集和选择是由自身抗原驱动的。