近日，美国西北大学Vipul Shukla及其小组发现，依赖于Arid1a的典型BAF复合物抑制炎症程序以驱动高效的生发中心B细胞反应。相关论文于2024年8月14日在线发表在《自然—免疫学》杂志上。

研究人员表示，哺乳动物的Brg1/Brm相关因子（BAF）复合物是核糖体重塑的主要调节因子，在包括生发中心（GC）衍生B细胞淋巴瘤在内的多种癌症中常发生突变。然而，不同的BAF复合物在GC B细胞生物学中的具体作用还不十分清楚。

研究人员发现含有富AT相互作用结构域1a（Arid1a）的典型BAF（cBAF）复合物是维持GC和高亲和力抗体反应所需的。缺失Arid1a的B细胞在进行初始激活时，无法维持GC程序。Arid1a为B细胞活化建立了可及性染色质景观，同时也是抑制炎症基因程序所需的。

Arid1a缺乏引发的炎症特征促进了中性粒细胞和炎性单核细胞的招募。通过阻断白细胞介素-1β或糖皮质激素受体激动剂来抑制炎症线索，可部分挽救Arid1a缺乏的GC，这突显了炎症在阻碍GC中的关键作用。该研究揭示了依赖Arid1a的cBAF在促进高效GC反应中的重要功能。

附：英文原文

Title: Arid1a-dependent canonical BAF complex suppresses inflammatory programs to drive efficient germinal center B cell responses

Author: Abraham, Ajay, Samaniego-Castruita, Daniela, Han, Isabella, Ramesh, Prathyaya, Tran, Mi Thao, Paladino, Jillian, Kligfeld, Heather, Morgan, Roxroy C., Schmitz, Rebecca L., Southern, Rebecca M., Shukla, Ashima, Shukla, Vipul

Issue&Volume: 2024-08-14

Abstract: The mammalian Brg1/Brm-associated factor (BAF) complexes are major regulators of nucleosomal remodeling that are commonly mutated in several cancers, including germinal center (GC)-derived B cell lymphomas. However, the specific roles of different BAF complexes in GC B cell biology are not well understood. Here we show that the AT-rich interaction domain 1a (Arid1a) containing canonical BAF (cBAF) complex is required for maintenance of GCs and high-affinity antibody responses. While Arid1a-deficient B cells undergo initial activation, they fail to sustain the GC program. Arid1a establishes permissive chromatin landscapes for B cell activation and is concomitantly required to suppress inflammatory gene programs. The inflammatory signatures instigated by Arid1a deficiency promoted the recruitment of neutrophils and inflammatory monocytes. Dampening of inflammatory cues through interleukin-1β blockade or glucocorticoid receptor agonist partially rescued Arid1a-deficient GCs, highlighting a critical role for inflammation in impeding GCs. Our work reveals essential functions of Arid1a-dependent cBAF in promoting efficient GC responses.

DOI: 10.1038/s41590-024-01920-y

Source: https://www.nature.com/articles/s41590-024-01920-y