Monte Carlo Study of B-Cell Receptor Clustering by Antigen Cross-Linking

Abstract

B cell signaling is triggered by the recognition of antigens by the surface proteins of the cell known as B-cell receptors (BCRs). It is known from experiments that, in the presence of soluble antigens BCRs assemble into small micro clusters and then structure into a macro cluster. However the underlying mechanisms of the antigen interaction with the BCRs and their cluster formation remain unclear. In our recent effort we have investigated, using Monte Carlo simulations, the mechanism of BCR clustering which would arise due to the intrinsic attractions among them. Such mutual attraction between two adjacent BCR molecules could arise, among other possibilities, due to cross-linking by bivalent soluble antigens. Recently, we have developed and studied a Monte Carlo model of B cell receptor clustering caused by binding and cross-linking of soluble antigens. The results of our study demonstrate the formation of small micro-clusters of BCR molecules (typically of size 2-10 molecules). But antigen cross-linking only is not adequate enough for the formation of large macro-clusters. A simple model of biased diffusion where BCR molecules experience a biased directed motion towards the largest cluster is then applied, which results in a single macro cluster of receptor molecules. The types of receptor clusters formed are analyzed using various network-based metrics such as the average distance between any pairs of receptors and number of adjacent pairs. The effect of BCR and antigen concentrations on the receptor clustering, the stability of the formed clusters over the time, and size of BCR-antigen cross-linked chains are all analyzed using suitable network-based metrics.