Anderson Shannon M, Tomayko Mary M, Ahuja Anupama, Haberman Ann M, Shlomchik Mark J
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
J Exp Med. 2007 Sep 3;204(9):2103-14. doi: 10.1084/jem.20062571. Epub 2007 Aug 13.
The study of murine memory B cells has been limited by small cell numbers and the lack of a definitive marker. We have addressed some of these difficulties with hapten-specific transgenic (Tg) mouse models that yield relatively large numbers of antigen-specific memory B cells upon immunization. Using these models, along with a 5-bromo-2'-deoxyuridine (BrdU) pulse-label strategy, we compared memory cells to their naive precursors in a comprehensive flow cytometric survey, thus revealing several new murine memory B cell markers. Most interestingly, memory cells were phenotypically heterogeneous. Particularly surprising was the finding of an unmutated memory B cell subset identified by the expression of CD80 and CD35. We confirmed these findings in an analogous V region knock-in mouse and/or in non-Tg mice. There also was anatomic heterogeneity, with BrdU(+) memory cells residing not just in the marginal zone, as had been thought, but also in splenic follicles. These studies impact the current understanding of murine memory B cells by identifying new phenotypes and by challenging assumptions about the location and V region mutation status of memory cells. The apparent heterogeneity in the memory compartment implies either different origins and/or different functions, which we discuss.
对小鼠记忆B细胞的研究一直受到细胞数量少和缺乏明确标志物的限制。我们利用半抗原特异性转基因（Tg）小鼠模型解决了其中一些难题，这些模型在免疫后能产生相对大量的抗原特异性记忆B细胞。利用这些模型，结合5-溴-2'-脱氧尿苷（BrdU）脉冲标记策略，我们在一项全面的流式细胞术研究中比较了记忆细胞与其初始前体细胞，从而揭示了几种新的小鼠记忆B细胞标志物。最有趣的是，记忆细胞在表型上具有异质性。特别令人惊讶的是发现了一个通过CD80和CD35表达鉴定的未发生突变的记忆B细胞亚群。我们在类似的V区敲入小鼠和/或非Tg小鼠中证实了这些发现。还存在解剖学上的异质性，BrdU(+)记忆细胞不仅如之前所认为的那样存在于边缘区，也存在于脾滤泡中。这些研究通过识别新的表型以及挑战关于记忆细胞位置和V区突变状态的假设，影响了当前对小鼠记忆B细胞的理解。记忆区明显的异质性意味着不同的起源和/或不同的功能，我们对此进行了讨论。
