Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, 3800 VIC, Australia; ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052 VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia.
ACRF Chemical Biology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, 3052 VIC, Australia; Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, 3800 VIC, Australia; Department of Medical Biology, The University of Melbourne, Parkville, 3010 VIC, Australia.
Cell Rep. 2021 Jul 20;36(3):109430. doi: 10.1016/j.celrep.2021.109430.
While the intrinsic apoptosis pathway is thought to play a central role in shaping the B cell lineage, its precise role in mature B cell homeostasis remains elusive. Using mice in which mature B cells are unable to undergo apoptotic cell death, we show that apoptosis constrains follicular B (FoB) cell lifespan but plays no role in marginal zone B (MZB) cell homeostasis. In these mice, FoB cells accumulate abnormally. This intensifies intercellular competition for BAFF, resulting in a contraction of the MZB cell compartment, and reducing the growth, trafficking, and fitness of FoB cells. Diminished BAFF signaling dampens the non-canonical NF-κB pathway, undermining FoB cell growth despite the concurrent triggering of a protective p53 response. Thus, MZB and FoB cells exhibit a differential requirement for the intrinsic apoptosis pathway. Homeostatic apoptosis constrains the size of the FoB cell compartment, thereby preventing competition-induced FoB cell atrophy.
虽然内源性凋亡途径被认为在塑造 B 细胞谱系中起着核心作用，但它在成熟 B 细胞稳态中的精确作用仍不清楚。我们利用成熟 B 细胞不能发生细胞凋亡的小鼠，表明凋亡限制了滤泡 B（FoB）细胞的寿命，但对边缘区 B（MZB）细胞的稳态没有作用。在这些小鼠中，FoB 细胞异常积累。这加剧了细胞间对 BAFF 的竞争，导致 MZB 细胞区室收缩，并减少 FoB 细胞的生长、迁移和适应性。BAFF 信号的减弱抑制了非经典 NF-κB 途径，尽管同时触发了保护性 p53 反应，但仍削弱了 FoB 细胞的生长。因此，MZB 和 FoB 细胞对内在凋亡途径表现出不同的需求。稳态凋亡限制了 FoB 细胞区室的大小，从而防止了竞争诱导的 FoB 细胞萎缩。
