Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA.
Nat Immunol. 2012 May 6;13(6):604-11. doi: 10.1038/ni.2294.
Antibody class defines function in B cell immunity, but how class is propagated into B cell memory remains poorly understood. Here we demonstrate that memory B cell subsets unexpectedly diverged across antibody class through differences in the effects of major transcriptional regulators. Conditional genetic deletion of the gene encoding the transcription factor T-bet selectively blocked the formation and antigen-specific response of memory B cells expressing immunoglobulin G2a (IgG2a) in vivo. Cell-intrinsic expression of T-bet regulated expression of the transcription factor STAT1, steady-state cell survival and transcription of IgG2a-containing B cell antigen receptors (BCRs). In contrast, the transcription factor RORα and not T-bet was expressed in IgA(+) memory B cells, with evidence that knockdown of RORα mRNA expression and chemical inhibition of transcriptional activity also resulted in lower survival and BCR expression of IgA(+) memory B cells. Thus, divergent transcriptional regulators dynamically maintain subset integrity to promote specialized immune function in class-specific memory B cells.
抗体类别决定了 B 细胞免疫的功能，但 B 细胞记忆如何通过主要转录调节剂的作用差异而传播到 B 细胞记忆仍知之甚少。在这里，我们证明了通过主要转录调节剂的作用差异，抗体类别出乎意料地使记忆 B 细胞亚群发生分歧。编码转录因子 T-bet 的基因条件性遗传缺失选择性地阻止了体内表达免疫球蛋白 G2a（IgG2a）的记忆 B 细胞的形成和抗原特异性反应。T-bet 的细胞内表达调节转录因子 STAT1、稳态细胞存活和包含 IgG2a 的 B 细胞抗原受体（BCR）的转录。相比之下，转录因子 RORα而不是 T-bet 在 IgA(+)记忆 B 细胞中表达，有证据表明 RORα mRNA 表达的敲低和转录活性的化学抑制也导致 IgA(+)记忆 B 细胞的存活率和 BCR 表达降低。因此，不同的转录调节剂动态地维持亚群完整性，以促进特定类别记忆 B 细胞的特异性免疫功能。
