MRC National Institute for Medical Research, London
Science for Health
Pavel Tolar group project:
Mechanisms of B-cell receptor activation by antigens
B-lymphocytes recognize antigens by sampling tissues with their uniquely recombined B-cell receptors (BCR). Binding of antigens to the BCR activates B cells, eventually leading to production of pathogen-specific antibodies.
Our work is focused on the initial steps of B cell activation by antigens. In particular, we are interested in the following questions:
How is BCR signaling organized in living B cells?
Antigen binding induces formation of BCR microclusters in the plasma membrane of B cells. These microclusters are important for BCR signaling and the capture of antigens.
We focus on the mechanism of assembly of the BCR into signaling microclusters and on the routes of entry of these microclusters into intracellular compartments.
We also investigate how abnormal microclustering of the BCR contributes to pathological signaling in human lymphomas.
BCR microclusters in the immune synapse
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BCR (green) in a B cell contacting an antigenic surface. BCR forms microclusters that are transported to the center of the synapse.
What is the structural basis of BCR activation by antigen binding?
We are interested in the structure of the BCR and in the changes induced in the BCR by antigen binding that initiate intracellular signaling. The BCR is composed of multiple subunits - the membrane immunoglobulin, which binds antigens, and the Igα-Igβ dimer, which initiates signaling.
Our initial studies are investigating the role of membrane-proximal domains of the BCR in the mechanism of signal transduction from the antigen binding sites to the intracellular signaling units. To visualize the activation of the BCR, we are imaging individual BCR molecules by single molecule fluorescence microscopy.
We hope to learn from these studies about the mechanisms by which B lymphocytes respond to various types of pathogens, including a range of epitopes present in the influenza virus.
Trajectory of a single B cell receptor molecule
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Single B-cell receptor molecule (green) stops to transduce an activation signal during engagement with antigen (red).
Tolar group
Recent publications
Research projects
- Mechanisms of B-cell receptor activation by antigens
Tolar biography
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