Holodick Nichol E, Rothstein Thomas L
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research , Manhasset, NY , USA.
Front Immunol. 2013 Dec 16;4:457. doi: 10.3389/fimmu.2013.00457.
Peritoneal B-1a cells manifest unusual signaling characteristics that distinguish them from splenic B-2 cells. These include the failure of BCR engagement to trigger NF-κB activation and DNA replication. Despite extensive study, a clear explanation for these characteristics has not emerged. Here we aim to develop a unified paradigm based on previous reports and recent results, which proposes a central role for phosphatase activity. We hypothesize B-1a cells are unable to induce NF-κB or proliferate after BCR cross-linking due to increased phosphatase abundance or activity. This phosphatase abundance and/or activity may be the result of unique B-1a cell characteristics such as increased levels of HSP70 and/or constitutive secretion of IL-10. We speculate phosphatase activity cannot be overcome by BCR ligation alone due to insufficient Vav protein expression, which does not allow for proper production of reactive oxygen species, which inhibit phosphatases. Furthermore, constitutively active Lyn also plays a negative regulatory role in B-1a. We expect that a new focus on phosphatase activity and its suppression will be revealing for BCR signal transduction in B-1 cells.
腹膜B-1a细胞表现出不同寻常的信号特征，这使其与脾脏B-2细胞相区别。这些特征包括BCR结合未能触发NF-κB激活和DNA复制。尽管进行了广泛研究，但尚未出现对这些特征的明确解释。在此，我们旨在基于先前的报道和近期的研究结果建立一个统一的范式，该范式提出磷酸酶活性起核心作用。我们假设B-1a细胞在BCR交联后无法诱导NF-κB或增殖，这是由于磷酸酶丰度或活性增加所致。这种磷酸酶丰度和/或活性可能是B-1a细胞独特特征的结果，如HSP70水平升高和/或IL-10的组成性分泌。我们推测，由于Vav蛋白表达不足，仅靠BCR连接无法克服磷酸酶活性，这使得无法产生适当的活性氧来抑制磷酸酶。此外，组成性激活的Lyn在B-1a细胞中也起负调节作用。我们预计，对磷酸酶活性及其抑制的新关注将有助于揭示B-1细胞中的BCR信号转导机制。
