Cell Collective28252000ModelsAkram Mendezhttps://cellcollective.org/#2394/b-cell-differentiation27.3978000000000041SBML1Cell Collectivehttps://cellcollective.org/#2394:1/b-cell-differentiationTerminal differentiation of B cells is an essential process for the humoral immune response in vertebrates and is achieved by the concerted action of several transcription factors in response to antigen recognition and extracellular signals provided by T-helper cells. While there is a wealth of experimental data regarding the molecular and cellular signals involved in this process, there is no general consensus regarding the structure and dynamical properties of the underlying regulatory network controlling this process. We developed a dynamical model of the regulatory network controlling terminal differentiation of B cells. The structure of the network was inferred from experimental data available in the literature, and its dynamical behavior was analyzed by modeling the network both as a discrete and a continuous dynamical systems. The steady states of these models are consistent with the patterns of activation reported for the Naive, GC, Mem, and PC cell types. Moreover, the models are able to describe the patterns of differentiation from the precursor Naive to any of the GC, Mem, or PC cell types in response to a specific set of extracellular signals. We simulated all possible single loss- and gain-of-function mutants, corroborating the importance of Pax5, Bcl6, Bach2, Irf4, and Blimp1 as key regulators of B cell differentiation process. The model is able to represent the directional nature of terminal B cell differentiation and qualitatively describes key differentiation events from a precursor cell to terminally differentiated B cells.A Network Model to Describe the Terminal Differentiation of B Cells.Méndez Akram A, Mendoza Luis LB-cell differentiation, B-lymphocyte differentiation, B lymphocyte differentiation., B cell developmentCell., terminal differentiationB-cell differentiation, B-lymphocyte differentiation, B lymphocyte differentiation., B cell developmentLSIRF, IPP2A2, d230, ZBTB27, MUM1, BTBD25, experimental, conformation, BTB and CNC homolog 2, Processes, KLP, BACH2, dTAFII250, Development, precursor, Transcription Factor, EfW1, terminal differentiation, laz3, dIKK-gamma, PHAPII, protrusion, 5730420M11Rik, dmTAF[[II]]230, znf51, dmTAF1, Taf230, DmIKK-gamma, Consensus, Antigen, Cell., dmIKKgamma, IKK[[gamma]], IKKg, ZNFPR1A1, KEY, Key, TAF250, EBB-1, SET, Spip, b2b1765Clo, Transcription, Taf200, Immune Responses, methods, dTAF[[II]]250, B-cell-specific transcription factor, B-lymphocyte differentiation, reference sample, TFIID TAF250, cel, TAF-I, cell, experimental section, ipp2a2, 2pp2a, Taf1p, CG10574, BSAP, DmelCG4299, Bach2, dTAF250, IGAAD, set, bcl5, Immune Response, 2PP2A, IKK, DmelCG10574, taf-ibeta, LAZ3, B lymphocyte differentiation, dSET, dSet, blimp1, Consensus Development, BCL5, Bcl5, Behaviors, TAF, Controlled, single-organism behavior, phapii, Controlling, dTAF[[II]]230, TAF[[II]]250, anatomical protrusion, Process, DmelCG10120, Blimp1, Humoral Immune Response, IRF-4, MDH, igaad, zbtb27, B-cell differentiation, TAF200, StF-IT-1, l(3)84Ab, Factor, BG:DS00004.13, function, ME, TAFII-250, TAF250/230, Cell, Acceptance Processes, group, dTAF230, Literatures, IKKgamma, Acceptance Process, AI385587, DmIKKgamma, Humoral Immunity, TAFII250, I-2PP2A, PAX5, dIKK, p230, E030004N02Rik, Dm I-2, vertebrates, I2PP2A, Kenny, TAF[[II]]250/230, Vertebrata, TFIID, Humoral, Vertebrate, ZNF51, Me, activation, BLIMP1, parent ion, Taf[[II]]250, Acceptance, Factors, TAF[[II]]230, HLA-DR-associated protein II, ensemble, DI-2, SHEP8, ALL3, Dmikkgamma, I-2Dm, Humoral Immune Responses, IKK-gamma, mem, TAF[II]250, men, CG4299, CG17603, CG16910, TAF[[II]], experimental procedures, I-2PP1, extracellular, dSET/TAF-Ibeta, 2610030F17Rik, bcl6a, DmelCG17603, TAF-IBETA, Blimp-1, PRDI-BF1, DmelCG16910, Humoral Immune, precursor ion, Taf250, spine, SR3-5, B cell development, xblimp1, Response, NF-EM5, anon-WO0118547.278, TAF-Ibeta, BCL6A, AA407739, i2pp2a, Pax-5, Mdh-NADP, TAF230, CG10120, TAF128252falseB cell differentiationA dynamic model for the regulatory network that controls terminal B cell differentiation2014-05-122016-01-272016-01-27239426751566