Paper Info
Title
A Network Model to Describe the Terminal Differentiation of B Cells
Abstract
Terminal 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.
Year
DOI
Venue
2016
10.1371/journal.pcbi.1004696
PLOS COMPUTATIONAL BIOLOGY
Keywords
Field
DocType
cell differentiation,dynamical systems,transcription factors
Precursor cell,Biology,B cell,Cellular differentiation,Cell type,BCL6,Dynamical systems theory,Signal transduction,Bioinformatics,Transcription factor
Journal
Volume
Issue
ISSN
12
1
1553-734X
Citations 
PageRank 
References 
3
0.47
4
Authors
2
Name
Order
Citations
PageRank
Akram Méndez130.47
luis mendoza227125.94