Molecular mechanisms insulating proliferation from genotoxic stress in B lymphocytes

Trends Immunol. 2023 Aug 10:S1471-4906(23)00134-5. doi: 10.1016/j.it.2023.06.010. Online ahead of print.ABSTRACTIn 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.PMID:37573227 | DOI:10.1016/j.it.2023.06.010
Source: Trends in Immunology - Category: Allergy & Immunology Authors: Source Type: research