Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation
Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation
复制标题
DOI：
10.1038/ni1016
复制
发表时间：
2004-01-01
影响因子：
30.5
通讯作者：
Hodgkin, PD
中科院分区：
文献类型：
--
作者：
Hasbold, J;Corcoran, LM;Hodgkin, PD
幼稚B淋巴细胞经过同型转换，发育为免疫球蛋白分泌细胞，产生有效免疫所需的适当种类和数量的抗体。虽然这看起来很复杂，但我们在这里报道，从幼稚前体产生免疫球蛋白g分泌细胞是高度可预测的。同型转换和发育为分泌细胞的概率随着细胞的连续分裂而变化，并独立地交织在一起。细胞因子改变每个分化事件的概率，同时保持其独立分类的完整性。结果，细胞分裂时，细胞异质性自动产生。随机分裂相关的异质性调控挑战了将不同表型与独特信号组合联系起来的传统范式，并有可能大大简化我们对免疫复杂性的概念。
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.