Hasbold Jhagvaral, Corcoran Lynn M, Tarlinton David M, Tangye Stuart G, Hodgkin Philip D
Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag Number 6, Newtown, NSW 2042, Australia.
Nat Immunol. 2004 Jan;5(1):55-63. doi: 10.1038/ni1016. Epub 2003 Nov 30.
Naive B lymphocytes undergo isotype switching and develop into immunoglobulin-secreting cells to generate the appropriate class and amount of antibody necessary for effective immunity. Although this seems complex, we report here that the generation of immunoglobulin G-secreting cells from naive precursors is highly predictable. The probabilities of isotype switching and development into secreting cells change with successive cell divisions and interleave independently. Cytokines alter the probability of each differentiation event, while leaving intact their independent assortment. As a result, cellular heterogeneity arises automatically as the cells divide. Stochastic division-linked regulation of heterogeneity challenges the conventional paradigms linking distinct phenotypes to unique combinations of signals and has the potential to simplify our concept of immune complexity considerably.
初始B淋巴细胞经历同种型转换并发育成分泌免疫球蛋白的细胞，以产生有效免疫所需的适当类别和数量的抗体。尽管这看起来很复杂，但我们在此报告，从初始前体细胞产生分泌免疫球蛋白G的细胞是高度可预测的。同种型转换和发育成分泌细胞的概率随着连续的细胞分裂而变化，并且独立交错。细胞因子改变每个分化事件的概率，同时保持它们的独立分类。结果，随着细胞分裂，细胞异质性自动出现。与随机分裂相关的异质性调节挑战了将不同表型与独特信号组合联系起来的传统范式，并有可能极大地简化我们对免疫复杂性的概念。
