Forschungsprojekte (Drittmittel)

Projekt

Do germinal centres interact via their produced antibodies?

Antibodies generated by the germinal centre output cells dilute over the whole organism. In particular, these antibodies may re-enter germinal centres and eventually influence the affinity maturation process.

In cooperation with the group of Kai Toellner (Birmingham, UK), we investigated this question in a combined experimental and theoretical approach and found that antibodies re-enter germinal centres in an affinity-dependent manner and that produced antibodies compete with germinal centre B cells for binding antigen.

Mathematical models showed that this competition accelerates affinity maturation by about 24 hours. The main impact seemed to be the initiation of the shutdown of the germinal centre reaction. A natural implication is that germinal centres may interact via their products. We want to understand whether this interaction leads to a synchronisation or an inhibition of germinal centres. This is of particular importance for the elderly population with frequent chronic inflammatory states. 

Penetration of antibodies into murine splenic germinal centres. a) Endogenous IgMb (red) is displaced by exogenous low affinity IgMa (green), which is replaced by endogenous IgMb (red) again after…

SIMM members

Alexey Uvarovskii (since 2016 in Heidelberg), Jaber Dehghany, Michael Meyer-Hermann

Publications

Zhang* Y, Meyer-Hermann* M, George L, Khan M, Figge MT, Falciani F, Kosco-Vilbois M, Toellner K-M. Germinal centre B cells govern their own fate via antibody feedback. J Exp Med 210 (2013) 457-464. [*shared first author]

Funding

BMBF-eMED: SYSIMIT
The Human Frontier Science Program Organization (HFSP)

    Projektleiter

    Beteiligte Gruppen

    Geldgeber / Förderer

    Sonstige

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