  The clustering of B cell receptor (BCR) molecules and the formation of the
protein segregation structure known as the immunological synapse appears to
precede antigen (Ag) uptake by B cells. The mature B cell synapse is
characterized by a central cluster of BCR/Ag molecular complexes surrounded by
a ring of LFA-1/ICAM-1 complexes. Recent experimental evidence shows receptor
clustering in B cells can occur via mechanical or signaling-driven processes.
An alternative mechanism of diffusion and affinity-dependent binding has been
proposed to explain synapse formation in the absence of signaling-driven
processes. In this work, we investigated the biophysical mechanisms that drive
immunological synapse formation in B cells across the physiological range of
BCR affinity (KA~10^6-10^10 M-1) through computational modeling. Our
computational approach is based on stochastic simulation of diffusion and
reaction events with a clearly defined mapping between probabilistic parameters
of our model and their physical equivalents. We show that a
diffusion-and-binding mechanism is sufficient to drive synapse formation only
at low BCR affinity and for a relatively stiff B cell membrane that undergoes
little deformation. We thus predict the need for alternative mechanisms: a
difference in the mechanical properties of BCR/Ag and LFA-1/ICAM-1 bonds and/or
signaling driven processes.
