Molecular mechanisms insulating proliferation from genotoxic stress in B lymphocytes.
Molecular mechanisms insulating proliferation from genotoxic stress in B lymphocytes.
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DOI：
10.1016/j.it.2023.06.010
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发表时间：
2023-08
影响因子：
16.8
通讯作者：
Nathaniel E. Wright;M. Mandal;M. Clark
中科院分区：
文献类型：
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作者：
Nathaniel E. Wright;M. Mandal;M. Clark
In mammals, B cells strictly segregate proliferation from somatic mutation as they develop within the bone marrow and then mature through germinal centers (GCs) in the periphery. Failure to do so risks autoimmunity and neoplastic transformation. Recent work has described how B cell progenitors transition between proliferation and mutation via cytokine signaling pathways, epigenetic chromatin regulation, and remodeling of 3D chromatin conformation. We propose a three-zone model of the GC that describes how proliferation and mutation are regulated. Using this model, we consider how recent mechanistic discoveries in B cell progenitors inform models of GC B cell function and reveal fundamental mechanisms underpinning humoral immunity, autoimmunity, and lymphomagenesis.
