Events controlling germinal centre onset
Germinal Centres are microanatomical structures forming upon an infection. The production of high affinity antibodies relies on the reaction taking place in the GC and is necessary for an efficient immune response against pathogens and for the success of vaccinations.
The initiation of the Germinal Centre relies on several factors such as antigen availability, proper activation and interaction of T and B cells, and B cell Receptor affinity. However, their interplay to generate an efficient germinal centre reaction remains unclear. Exploiting spatio-temporal simulations of the Germinal Centre reaction obtained with an agent-based model, we aim at understanding the interaction of these factors in a healthy environment and the relation between failure of these mechanisms and pathological conditions.
T cells have several crucial functions in the development of functional Germinal Centres. Specifically, activation and subsequent differentiation of B cells rely on the interaction with follicular helper T cells. However, the latter needs to be regulated to avoid development of pathological conditions such as autoimmune diseases. We use an agent-based model to describe the dynamics of follicular helper T cells and to analyse how it influences the Germinal Centre reaction.
This project is carried out with the COSMIC consortium. The collaboration with the other groups involved will allow experimental validation of the results produced in silico and the mechanisms proven effective in silico will be used to investigate new treatment strategies.
Theinmozi Arulraj, Sebastian Binder, Philippe Robert (former member), Tanmay Mitra, Arnab Bandyopadhyay, Michael Meyer-Hermann
Antoine van Kampen (Amsterdam Medical Centre), Stefano Casola (IFOM Milan), Rikard Holmdahl (Karolinska Institutet), Dinis Calado (Francis Crick Institute), Michelle Linterman (Babraham Institute)
Roco JA, Mesin L, Binder SC, Nefzger C, Gonzalez-Figueroa P, Canete PF, Ellyard J, Shen Q, Robert PA, Cappello J, Vohra H, Zhang Y, Schiepers A, Toellner K-M, Polo J, Meyer-Herman M, Victora G, Vinuesa CG. Determining the timing and location of class switch recombination during T-dependent immune responses. Immunity 2019 Aug 20; 51: 337-350.
Cañete PF, Sweet RA, Gonzalez-Figueroa P, Papa I, Ohkura N, Bolton H, Roco JA, Cuenca M, Bassett KJ, Sayin I, Barry E, Lopez A, Canaday DH, Meyer-Herman M, Doglioni C, de St Groth BF, Sakaguchi S, Cook MC, Vinuesa CG. Regulatory roles of IL-10-producing human follicular T cells. J Exp Med 2019 Aug 5; 216(8): 1843-1856.
Nakagawa R, Leyland R, Meyer-Hermann M, Lu D, Turner M, Arbore G, Phan TG, Brink R, Vigorito E. MicroRNA-155 controls affinity-based selection by protecting c-Myc+ B-cells from apoptosis. J Clin Invest 126 (2016) 377-388.
Meyer-Hermann M, Mohr E, Pelletier N, Zhang Y, Victora GD, Toellner K-M. A theory of germinal center B cell selection, division and exit. Cell Reports 2 (2012) 162-174.
Victora GD, Schwickert TA, Fooksman DR, Meyer-Hermann M, Dustin ML, Nussenzweig MC. Germinal center selection mechanism revealed by multiphoton microscopy using a photoactivatable fluorescent reporter. Cell 143 (2010) 592-605.
Meyer-Hermann M, Maini PK, Iber D. An analysis of B cell selection mechanisms in germinal centers. Math Med Biol 23 (2006) 255-277.
EU Horizon 2020, Human Frontier Science Program
- System-Immunologie- Prof. Dr. Michael Meyer-Hermann