The effect of B cell receptor affinity on lipid mediated B cell receptor antigen microclustering (109.1)

Abstract After encountering antigens (Ags), B-cell receptors(BCRs) with bound Ags assemble into microclusters then into a macrocluster. BCR recognition of antigen results in a monotonically increasing graded signaling response with increasing affinity for Ag, a robust feature that seems to be characterizing BCR-Ag affinity discrimination. Recent experiments indicate an important role of very early (within seconds) signaling events, such as formation of BCR-Ag microclusters, in this affinity discrimination process. Our current studies improve upon our most recent biophysical models for BCR-Ag microcluster and macrocluster formation by incorporating lipid-mediated BCR attraction factors. We examine the effect of (a) lipid and BCR concentration, and (b) varying attractive forces between different lipid and BCR pairings. Our studies indicate that a weak attraction between pairs of BCR molecules does not lead to microclusters. However, strong coupling between BCR and lipid (sphingolipids) molecules, that possibly arises upon antigen binding, generates microclusters of size similar to what has been observed in experiments. Our results indicate that microcluster size and number increase with increasing affinity while the formation times of such early BCR-Ag clusters decrease. These features can have important implications for the B cell affinity discrimination problem.