Kaku Hiroaki, Holodick Nichol E, Tumang Joseph R, Rothstein Thomas L
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY, United States.
Compass Therapeutics LLC, Cambridge, MA, United States.
Front Immunol. 2017 Jun 20;8:672. doi: 10.3389/fimmu.2017.00672. eCollection 2017.
B-1a cells are innate-like B-lymphocytes producing natural antibodies. Activation-induced cytidine deaminase (AID), a product of the gene, plays a central role in class-switch recombination and somatic hypermutation in B cells. Although a role for in B-1a cells has been suggested on the basis of experiments with knock out (KO) mice, whether B-1a cells express , and if so, which B-1a cell subpopulation expresses , remains unknown. Here, we demonstrate that B-1 cells express , but at a level below that expressed by germinal center (GC) B cells. We previously reported that B-1a cells can be subdivided based on CD25 expression. We show here that B-1a cell expression is concentrated in the CD25 B-1a cell subpopulation. These results suggest the possibility that previous studies of memory B cells identified on the basis of expression may have inadvertently included an unknown number of CD25 B-1a cells. Although B-1a cells develop normally in the absence of , a competitive reconstitution assay reveals enhanced vigor for AID KO B-1a cell bone marrow (BM) progenitors, as compared with wild-type BM B-1 cell progenitors. These results suggest that AID inhibits the development of B-1a cells from BM B-1 cell progenitors in a competitive environment.
B-1a细胞是产生天然抗体的固有样B淋巴细胞。激活诱导的胞苷脱氨酶(AID)是该基因的产物,在B细胞的类别转换重组和体细胞超突变中起核心作用。尽管基于基因敲除(KO)小鼠的实验提示了AID在B-1a细胞中的作用,但B-1a细胞是否表达AID,以及如果表达的话,哪个B-1a细胞亚群表达AID,仍然未知。在这里,我们证明B-1细胞表达AID,但表达水平低于生发中心(GC)B细胞。我们之前报道过B-1a细胞可根据CD25表达进行细分。我们在此表明B-1a细胞的AID表达集中在CD25+B-1a细胞亚群中。这些结果提示,先前基于AID表达鉴定记忆B细胞的研究可能无意中包含了数量未知的CD25+B-1a细胞。尽管在没有AID的情况下B-1a细胞正常发育,但一项竞争性重建试验显示,与野生型骨髓B-1细胞祖细胞相比,AID基因敲除的B-1a细胞骨髓(BM)祖细胞活力增强。这些结果表明,在竞争环境中,AID抑制骨髓B-1细胞祖细胞向B-1a细胞的发育。