MEF2B (myocyte enhancer factor 2B) is a transcriptional activator that binds to the MEF2 DNA element to regulate gene expression in multiple cell types. In B cells specifically, MEF2B promotes germinal center (GC) B cell differentiation and functions as a critical component of the BCL6 transcriptional complex, supporting GC-DLBCL (germinal center diffuse large B-cell lymphoma) cell growth 1. MEF2B cooperates with histone acetyltransferases CREBBP and EP300 in chr19 remodeling 2. The gene is frequently mutated in B-cell lymphomas; N-terminal mutations escape transcriptional repression, while C-terminal mutations enhance protein stability and transcriptional activity by impairing phosphorylation-dependent ubiquitin-mediated degradation and increasing SWI/SNF complex interaction 3. These mutations drive GC B-cell lymphomagenesis, particularly in follicular lymphoma and DLBCL 45. Clinically, MEF2B mutations are incorporated into prognostic models (m7-FLIPI) that improve risk stratification for follicular lymphoma patients receiving immunochemotherapy, with mutations associated with treatment failure 6. Additionally, MEF2B is a direct target of Epstein-Barr virus nuclear antigen 1 (EBNA1) and is essential for EBV-infected B-lymphocyte survival 7, while ZEB2-mediated MEF2B repression promotes age-associated B cell formation in autoimmunity 8.