Abstract
Germinal centers host a mini-evolutionary environment where B cells can mutate their receptor and be selected depending on its affinity to target antigens in a process called affinity maturation. Starting from founder cells with a weak B cell receptor affinity, germinal centers release output cells as antibody-secreting cells or memory cells with a very high affinity, a property which is essential for pathogen clearance and immune memory. Therapeutic interventions on the germinal centers are tantalizing approaches to improve vaccines or to support rejection of chronic pathogens such as HIV. However, the complexity of the selection processes makes it very hard to make reliable predictions. Here, we present in detail how to build an agent-based model (hyphasma), accounting for the dynamics of the germinal center. It encompasses the core quantitative traits of affinity maturation, and allowed to make reliable predictions in previous studies.
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References
Tas JM et al (2016) Visualizing antibody affinity maturation in germinal centers. Science. doi:10.1126/science.aad3439
Vinuesa CG, Linterman MA, Goodnow CC, Randall KL (2010) T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol Rev 237:72–89
Thaunat O et al (2012) Asymmetric segregation of polarized antigen on B cell division shapes presentation capacity. Science 335:475–479
Dustin ML, Meyer-Hermann M (2012) Antigen feast or famine. Science 335:408–409
Allen CD et al (2004) Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5. Nat Immunol 5:943–952
Meyer-Hermann M (2014) Overcoming the dichotomy of quantity and quality in antibody responses. J Immunol 193:5414–5419
Gitlin AD, Shulman Z, Nussenzweig MC (2014) Clonal selection in the germinal centre by regulated proliferation and hypermutation. Nature 509:637–640
Meyer-Hermann M et al (2012) A theory of germinal center B cell selection, division, and exit. Cell Rep 2:162–174
Meyer-Hermann ME, Maini PK (2005) Interpreting two-photon imaging data of lymphocyte motility. Phys Rev E 71:061912
Linterman MA et al (2009) Follicular helper T cells are required for systemic autoimmunity. J Exp Med 206:561–576
De Vinuesa CG et al (2000) Germinal centers without T cells. J Exp Med 191:485–494
Baumjohann D et al (2013) Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype. Immunity 38:596–605
Perelson AS, Oster GF (1979) Theoretical studies of clonal selection: minimal antibody repertoire size and reliability of self-non-self discrimination. J Theor Biol 81:645–670
Meyer-Hermann M, Deutsch A, Or-Guil M (2001) Recycling probability and dynamical properties of germinal center reactions. J Theor Biol 210:265–285
Victora GD et al (2010) Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143:592–605
Allen CD, Okada T, Tang HL, Cyster JG (2007) Imaging of germinal center selection events during affinity maturation. Science 315:528–531
Figge MT et al (2008) Deriving a germinal center lymphocyte migration model from two-photon data. J Exp Med 205:3019–3029
Meyer-Hermann ME, Maini PK, Iber D (2006) An analysis of B cell selection mechanisms in germinal centers. Math Med Biol 23:255–277
Duchez S, Rodrigues M, Bertrand F, Valitutti S (2011) Reciprocal polarization of T and B cells at the immunological synapse. J Immunol 187:4571–4580
Zhang Y et al (2013) Germinal center B cells govern their own fate via antibody feedback. J Exp Med 210:457–464
Schwickert TA et al (2007) In vivo imaging of germinal centres reveals a dynamic open structure. Nature 446:83–87
Hauser AE et al (2007) Definition of germinal-center B cell migration in vivo reveals predominant intrazonal circulation patterns. Immunity 26:655–667
Nakagawa R et al (2015) MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis. J Clin Invest 126
Garin A et al (2010) Toll-like receptor 4 signaling by follicular dendritic cells is pivotal for germinal center onset and affinity maturation. Immunity 33:84–95
He J-S et al (2013) The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response. J Exp Med 210:2755–2771
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Robert, P.A., Rastogi, A., Binder, S.C., Meyer-Hermann, M. (2017). How to Simulate a Germinal Center. In: Calado, D. (eds) Germinal Centers. Methods in Molecular Biology, vol 1623. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7095-7_22
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DOI: https://doi.org/10.1007/978-1-4939-7095-7_22
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