The network of receptors characterize B cell receptor micro- and macroclustering in a monte carlo model

During the recognition of soluble antigens, B cell receptors (BCR) are known to form signaling clusters that can crucially modulate intracellular activation pathways and B cell response. Little is known about the precise nature of receptor cluster and its formation mechanism for the case of soluble antigens. Initial experiments have shown that B cell receptors first microcluster upon ligation with soluble antigens, and then coarsen into a macroscopic cap structure at one pole of a B cell. Such a mutual receptor-receptor attraction can arise locally due to cross-linking by soluble antigens among other possibilities. We develop an energy based Monte Carlo model to investigate the mechanism of B-cell receptor clustering upon ligation with soluble antigens. Our results show that mutual attraction between nearest neighbor receptor pairs can lead to microclustering of B cell receptors, but it is not sufficient for receptor macroclustering. A simple model of biased diffusion where BCR molecules experience a biased directed motion toward the largest cluster is then applied, which results in a single macrocluster of receptor molecules. The various types of receptor clusters are analyzed using the developed network-based metrics such as the average distance between any pairs of receptors. © 2010 American Chemical Society.