体细胞突变
生发中心
生物
人口
细胞生物学
体细胞
遗传学
B细胞
抗体
基因
社会学
人口学
作者
Domenick E. Kennedy,Michael K. Okoreeh,Mark Maienschein‐Cline,Junting Ai,Margaret Veselits,Kaitlin C. McLean,Yogesh Dhungana,Hong Wang,Junmin Peng,Hongbo Chi,Malay Mandal,Marcus R. Clark
标识
DOI:10.1038/s41590-020-0660-2
摘要
Within germinal centers (GCs), complex and highly orchestrated molecular programs must balance proliferation, somatic hypermutation and selection to both provide effective humoral immunity and to protect against genomic instability and neoplastic transformation. In contrast to this complexity, GC B cells are canonically divided into two principal populations, dark zone (DZ) and light zone (LZ) cells. We now demonstrate that, following selection in the LZ, B cells migrated to specialized sites within the canonical DZ that contained tingible body macrophages and were sites of ongoing cell division. Proliferating DZ (DZp) cells then transited into the larger DZ to become differentiating DZ (DZd) cells before re-entering the LZ. Multidimensional analysis revealed distinct molecular programs in each population commensurate with observed compartmentalization of noncompatible functions. These data provide a new three-cell population model that both orders critical GC functions and reveals essential molecular programs of humoral adaptive immunity. Germinal centers are typically divided into dark and light zones. Clark and colleagues identify ‘gray zone’ cyclin B1+ B cell clusters as sites of ongoing cell proliferation, and these cells are distinct from dark zone B cells that undergo AID-dependent somatic hypermutation. This separation of function safeguards B cells undergoing DNA replication against potential mutagenic events that could result in neoplastic transformation.
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