Gagro Alenka, Servis Drazen, Cepika Alma-Martina, Toellner Kai-Michael, Grafton Gillian, Taylor Dale R, Branica Srecko, Gordon John
Institute of Immunology, Zagreb, Croatia.
Immunology. 2006 May;118(1):66-77. doi: 10.1111/j.1365-2567.2006.02342.x.
B cells bifurcating along 'type 1' or 'type 2' pathways under the influence of polarizing cytokines can, in turn, influence the direction of an immune response. Here, we compare the capacity of human B cells residing within naïve and memory compartments to participate in type 1 polarizing responses. B-cell receptor (BCR) engagement provided the main signal for interleukin (IL)-12Rbeta1 expression in the two subsets: this was potentiated by CD154 together with interferon-gamma (IFN-gamma) but inhibited by IL-12. IL-12Rbeta2 could be induced on a minority of B cells by the same signals, and also by IFN-gamma alone. WSX-1, a receptor for IL-27, was expressed in both subsets with no evidence for its regulation by the signals studied. While neither subset was capable of secreting much IL-12 p70, memory B cells could produce a small amount of IL-12 p40 on CD40 ligation. Memory B cells also, exclusively, expressed IL-23 p19 mRNA on BCR triggering. Importantly, products of appropriately stimulated memory--but not naive--B cells were shown to promote the synthesis of IFN-gamma in uncommitted T-helper cells. The data indicate an equal capacity for naïve and memory B cells to respond within a type 1 polarizing environment. Although poorly equipped for initiating type 1 responses, B cells--by virtue of the memory subset--reveal a capacity for their maintenance and amplification following T-dependent signalling.
在极化细胞因子的影响下,沿着“1型”或“2型”途径分化的B细胞反过来可以影响免疫反应的方向。在此,我们比较了存在于初始和记忆区室中的人类B细胞参与1型极化反应的能力。B细胞受体(BCR)的激活为两个亚群中白细胞介素(IL)-12Rβ1的表达提供了主要信号:CD154与干扰素-γ(IFN-γ)共同作用可增强该信号,但IL-12会抑制该信号。相同信号以及单独的IFN-γ可诱导少数B细胞表达IL-12Rβ2。IL-27的受体WSX-1在两个亚群中均有表达,未发现所研究的信号对其有调节作用。虽然两个亚群都不能分泌大量的IL-12 p70,但记忆B细胞在CD40连接时可产生少量的IL-12 p40。记忆B细胞在BCR触发时也仅表达IL-23 p19 mRNA。重要的是,适当刺激的记忆B细胞(而非初始B细胞)的产物可促进未分化的辅助性T细胞合成IFN-γ。数据表明,在1型极化环境中,初始B细胞和记忆B细胞有同等的反应能力。尽管启动1型反应的能力较差,但B细胞凭借记忆亚群在T细胞依赖性信号传导后显示出维持和放大该反应的能力。