Kretschmer Karsten, Stopkowicz Jana, Scheffer Stephan, Greten Tim F, Weiss Siegfried
Molecular Immunology, Gesellschaft für Biotechnologische Forschung, German Research Centre for Biotechnology, Braunschweig, Germany.
J Immunol. 2004 Jul 1;173(1):197-204. doi: 10.4049/jimmunol.173.1.197.
Positive selection by autoantigens is believed to play an important role in the generation/maintenance of B-1a cells. Recently, it has been described that splenectomy results in the loss of an already established B-1a cell pool. To elucidate whether the spleen influences the peritoneal B-1a repertoire, we have analyzed the consequences of splenectomy in the recently established IgL-transgenic L2 mouse model. L2 mice are characterized by a severe block of B-2 development and predominance of B-1a cells, which exhibit a pronounced IgH oligoclonality, presumably due to positive selection by autoantigens. In this study, we show that, in striking contrast to splenectomized normal mice, L2 mice exhibit unchanged frequencies of peritoneal B-1a cells. The IgH repertoire of these B-1a cells, however, was severely perturbed in that the previously described predominant B-1a H chains were no longer present. The repertoire changes were partial since phosphatidylcholine-specific B-1a cells were present in similar numbers before and after splenectomy. Thus, splenic Ags appear to act as "survival factors" for major subsets of peritoneal B cells. The loss of B-1a cells in the absence of such factors is compensated by repertoire changes among B-1a cells in B cell lymphopenic L2 but not normal mice.
自身抗原的阳性选择被认为在B-1a细胞的产生/维持中起重要作用。最近,有描述称脾切除会导致已建立的B-1a细胞池丧失。为了阐明脾脏是否影响腹膜B-1a细胞库,我们分析了在最近建立的IgL转基因L2小鼠模型中脾切除的后果。L2小鼠的特征是B-2细胞发育严重受阻且B-1a细胞占优势,这些B-1a细胞表现出明显的IgH寡克隆性,推测是由于自身抗原的阳性选择。在本研究中,我们发现,与脾切除的正常小鼠形成鲜明对比的是,L2小鼠腹膜B-1a细胞的频率未发生变化。然而,这些B-1a细胞的IgH细胞库受到严重干扰,因为先前描述的主要B-1a重链不再存在。由于脾切除前后磷脂酰胆碱特异性B-1a细胞数量相似,所以细胞库变化是部分性的。因此,脾脏抗原似乎充当腹膜B细胞主要亚群的“存活因子”。在缺乏此类因子的情况下,B-1a细胞的丧失在B细胞淋巴细胞减少的L2小鼠而非正常小鼠中通过B-1a细胞之间的细胞库变化得到补偿。