Results from modeling of B-Cell receptors binding to antigen.
In the late 80's, Dintzis et al. conducted an experiment which showed that T-Cell independent activation of B-cells needs high-valence antigen and happens only in a narrow range of antigen concentration. These experiments were believed to be explained by the "immunon" theory that requires that a minimum number of receptors need to be cross-linked to activate a cell. However, the immunon theory does not take into account receptor dynamics and cannot explain the lack of immune response at high antigen concentration or low antigen valence. We propose instead a simple, new mechanism for the T-Cell independent activation of B-Cell, which includes receptor endocytosis. Our model focuses on the fact that for the majority of antigens where the B-Cell is activated with T-Cell help, the kinetic parameters for binding, unbinding and endocytosis must be tuned so that there is an equilibrium between the number of receptors bound on the surface of the B-Cell and the number of antigen-bound receptors endocytosed. This equilibrium mechanism is probably generic and will also occur even when the B-Cell is activated by antigen without T-Cell help. By computer modeling, we show that if we accept this hypothesis of the requirement for equilibrium between the two mechanisms of binding and endocytosis, then we can explain both the valence cutoff and the low and high zone tolerance seen in the Dintzis experiment.
Bhanot
Gyan
G
Computational Biology Center, T.J.WatsonResearch Center, IBM Research, Yorktown Height, NY 10598, USA. gyan@us.ibm.com, gyan@ias.edu
D000222:Adaptation, Physiological / Q000276:immunology; D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000937:Antigen-Antibody Reactions / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology*; D003198:Computer Simulation; D004705:Endocytosis / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D018448:Models, Immunological; D025941:Protein Interaction Mapping / Q000379:methods; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D000936:Antigen-Antibody Complex; D011947:Receptors, Antigen, B-Cell