BTG1 mutation yields supercompetitive B cells primed for malignant transformation
Mlynarczyk C, Teater M, Pae J, Chin C, Wang L, Arulraj T, Barisic D, Papin A, Hoehn K, Kots E, Ersching J, Bandyopadhyay A, Barin E, Poh H, Evans C, Chadburn A, Chen Z, Shen H, Isles H, Pelzer B, Tsialta I, Doane A, Geng H, Rehman M, Melnick J, Morgan W, Nguyen D, Elemento O, Kharas M, Jaffrey S, Scott D, Khelashvili G, Meyer-Hermann M, Victora G, Melnick A. BTG1 mutation yields supercompetitive B cells primed for malignant transformation. Science 2023, 379: eabj7412. PMID: 36656933, PMCID: PMC10515739, DOI: 10.1126/science.abj7412.Peer-Reviewed Original ResearchConceptsGerminal center B cellsPositive selection signalsB-cell fitnessCell fitnessUnicellular organismsB cellsMulticellular lifeNatural selectionSelection signalsInduction kineticsGatekeeper mechanismAdaptive immune systemAltruistic cooperationNew mouse modelNormal counterpartsHuman lymphomasAntibody affinity maturationCellsInvasive lymphomaClinical outcomesMouse modelImmune systemMalignant transformationSupercompetitorsAffinity maturationCyclin D3 drives inertial cell cycling in dark zone germinal center B cells
Pae J, Ersching J, Castro T, Schips M, Mesin L, Allon S, Ordovas-Montanes J, Mlynarczyk C, Melnick A, Efeyan A, Shalek A, Meyer-Hermann M, Victora G. Cyclin D3 drives inertial cell cycling in dark zone germinal center B cells. Journal Of Experimental Medicine 2020, 218: e20201699. PMID: 33332554, PMCID: PMC7754672, DOI: 10.1084/jem.20201699.Peer-Reviewed Original ResearchConceptsGC B cellsB cellsGerminal centersExpansion of GC B cellsDose-dependentlyClonal B-cell lymphoproliferationGerminal center B cellsB-cell lymphoproliferationCyclin D3Gain-of-function mutationsCell cycle regulator cyclin D3Cell cycle programAffinity-dependent selectionLight zoneMalignant transformationClonal expansionOld miceVigorous proliferationCell cycleSomatic hypermutationCCND3 genesAffinity maturationDark zoneProliferationCyclinGerminal center‐derived lymphomas: The darkest side of humoral immunity
Mlynarczyk C, Fontán L, Melnick A. Germinal center‐derived lymphomas: The darkest side of humoral immunity. Immunological Reviews 2019, 288: 214-239. PMID: 30874354, PMCID: PMC6518944, DOI: 10.1111/imr.12755.Peer-Reviewed Original ResearchConceptsB cellsGC reactionGerminal centersImmune receptor signalingBCL6 transcription factorTreated lymphoma patientsB-cell neoplasmsFunction of BCL6GC-derived lymphomasImmune regulatory mechanismsMutations of genesGC B cellsClonal diversityTranscription factorsBiological themesEpigenetic regulationGenomic lesionsPoint mutationsRegulatory mechanismsEpigenetic programmingLymphoma patientsOncogenic functionEpigenetic standpointTumor-suppressive effectsMutations