首页|表观遗传印迹记录的记忆B细胞免疫刺激历史决定记忆B细胞的再分化命运

表观遗传印迹记录的记忆B细胞免疫刺激历史决定记忆B细胞的再分化命运

扫码查看
原文链接
  • NETL
  • NSTL
  • 万方数据
记忆B细胞是长期体液免疫的重要组成部分.在再次被同样的病原体感染之后,记忆B细胞可以迅速转变为产生抗体的浆细胞,或者重新进入生发中心(GCs)进行进一步的抗体体细胞高频突变和亲和力成熟.记忆B细胞重新参与生发中心反应对于产生针对流感病毒和HIV等高度变异病毒的广谱中和抗体至关重要.有报道显示记忆B细胞在抗原再刺激后的分化命运与不同的抗体种型和表面分子相关.然而,转录和表观遗传机制是否影响了这些记忆B细胞的命运尚不清楚.该研究发现,记忆B细胞经历的每次刺激都会以依赖于干扰素调节因子4(IRF4)的方式在表观遗传学上进行记录,这决定了B细胞中两个拮抗转录因子BLIMP1和BACH2的相对水平,进而影响了记忆B细胞在重新刺激时进入生发中心或成为浆细胞的可能性.
Past Antigen Exposures are Epigenetically Imprinted and Determine the Memory B Cell Fate Upon Rechallenge
Memory B cells are crucial components of long-term humoral immunity.Upon antigen re-exposure,memory B cells can rapidly become antibody-producing plasma cells or they can re-enter GCs(germinal centers)to undergo further antibody somatic hypermutation and affinity maturation.Memory B cell re-participation in the GC reaction is thought to be important for generating broadly neutralizing antibodies against highly mutating viruses such as influenza virus and HIV.The fate of memory B cells into plasma cells or GC B cells following an-tigen re-stimulation is associated with distinct antibody isotypes and memory B cell surface phenotypes.However,whether these memory B cell fates are intrinsically programmed by transcriptional and epigenetic mechanisms was not understood.This study finds that each stimulation experienced by memory B cells is epigenetically recorded in an IRF4-dependent manner,which determines the relative levels of two antagonistic transcription factors BLIMP1 and BACH2 in B cells,and in turn dictates the likelihood that a memory B cell enters a germinal center or becomes a plasma cell upon re-stimulation.

memory B cellimmune memorygerminal centerplasma cellcell differentiationepigenetic regulation

邵雯、祁海

展开 >

清华-北大生命科学联合中心,北京 100084

动态免疫学实验室,清华大学免疫所,北京 100084

清华大学基础医学院,北京 100084

昌平实验室,北京 102206

展开 >

记忆B细胞 免疫记忆 生发中心 浆细胞 细胞分化 表观遗传调控

科技部国家重点研发计划国家自然科学基金国家自然科学基金国家自然科学基金国家自然科学基金中国博士后科学基金北京市科学技术委员会新基石项目

2018YFE0200300318300238162100231900629322007252022T150351Z181100001318005NCI202244

2024

10.11844/cjcb.2024.09.0001

中国细胞生物学学报
中国科学院上海生命科学研究院,生物化学与细胞生物学研究所,中国细胞生物学学会

中国细胞生物学学报

CSTPCD
影响因子：0.554
ISSN：1674-7666
年,卷(期)：2024.46(9)