近日，美国匹兹堡大学Mark Shlomchik及其研究团队发现，记忆性B细胞亚群具有不同的发育起源，这些起源与不同的印记表观遗传状态相关联。2024年1月10日，《自然—免疫学》杂志在线发表了这项成果。

研究人员表示，记忆B细胞（MBC）在表型和功能上多种多样，但其发育起源仍未确定。小鼠MBC可根据CD80和PD-L2的表达分为不同的亚群。再免疫后，CD80/PD-L2双阴性（DN）的MBC会产生生殖中心B细胞（GCBC），而CD80/PD-L2双阳性（DP）的MBC会产生浆细胞，但不会产生GCBC。

研究人员采用多种方法（包括生成诱导型GCBC谱系报告小鼠）证明，在T细胞依赖性反应中，DN细胞的形成独立于生发中心 (GC)，而DP细胞则表现出滤泡外（DP_EX）或GCBC（DP_GC）起源。染色质和转录谱分析显示，DN细胞与早期记忆前体相似。

从对等的角度看，GCBC衍生的DP细胞与GCBC具有明显的基因组特征，而DPEX细胞则具有混合特征。再刺激时，DP_EX细胞更容易分裂，而DP_GC细胞则向IgG1⁺浆细胞分化。因此，MBC的功能多样性是通过不同的发育历史产生的，这种发育历史将特征性的表观遗传模式印刻在其后代身上，从而使它们产生不同的功能反应。

附：英文原文

Title: Memory B cell subsets have divergent developmental origins that are coupled to distinct imprinted epigenetic states

Author: Callahan, Derrick, Smita, Shuchi, Joachim, Stephen, Hoehn, Kenneth, Kleinstein, Steven, Weisel, Florian, Chikina, Maria, Shlomchik, Mark

Issue&Volume: 2024-01-10

Abstract: Memory B cells (MBCs) are phenotypically and functionally diverse, but their developmental origins remain undefined. Murine MBCs can be divided into subsets by expression of CD80 and PD-L2. Upon re-immunization, CD80/PD-L2 double-negative (DN) MBCs spawn germinal center B cells (GCBCs), whereas CD80/PD-L2 double-positive (DP) MBCs generate plasmablasts but not GCBCs. Using multiple approaches, including generation of an inducible GCBC-lineage reporter mouse, we demonstrate in a T cell-dependent response that DN cells formed independently of the germinal center (GC), whereas DP cells exhibited either extrafollicular (DPEX) or GCBC (DPGC) origins. Chromatin and transcriptional profiling revealed similarity of DN cells with an early memory precursor. Reciprocally, GCBC-derived DP cells shared distinct genomic features with GCBCs, while DPEX cells had hybrid features. Upon restimulation, DPEX cells were more prone to divide, while DPGC cells differentiated toward IgG1+ plasmablasts. Thus, MBC functional diversity is generated through distinct developmental histories, which imprint characteristic epigenetic patterns onto their progeny, thereby programming them for divergent functional responses.

DOI: 10.1038/s41590-023-01721-9

Source: https://www.nature.com/articles/s41590-023-01721-9