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Monte Carlo study of B-cell receptor clustering mediated by antigen crosslinking and directed transport

Cellular & Molecular Immunology volume 8, pages 255–264 (2011)Cite this article

Abstract

It is known from experiments that in the presence of soluble antigen, B-cell receptors (BCRs) assemble into microclusters and then collect into a macrocluster known as a ‘cap’. However, the mechanisms of BCR cluster formation during recognition of soluble antigens remain unclear. In previous work, we demonstrated that effective intrinsic attractions among BCRs can lead to the formation of small microclusters of BCR molecules. The effective intrinsic attractions could be caused by multivalent antigen binding, association with lipid rafts, or other biochemical factors. In the present study, we have developed and studied a Monte Carlo model of BCR clustering mediated by explicit binding and crosslinking of soluble bivalent antigens. Antigen crosslinking is shown to microcluster BCRs in an affinity-dependent manner and also in a biologically relevant timescale; however, antigen crosslinking alone does not appear to be sufficient for the formation of a single macrocluster of receptor molecules. We show that directed transport of BCRs is needed to drive the formation of large macroclusters. We constructed a simple model of directed transport, where BCR molecules diffuse towards the largest cluster or towards a random BCR microcluster, which results in a single macrocluster of receptor molecules. The mechanisms for both types of directed transport are compared using network-based metrics. We also develop and use appropriate network measures to analyze the effect of BCR and antigen concentration on BCR clustering, the stability of the formed clusters over time and the size of BCR–antigen crosslinked chains.

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Acknowledgements

ASR, PKT and SR are supported from National Institutes of Health grant AI074022. The results obtained with different binding strength values (K), and considering the eight neighboring nodes are reported in supporting information.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of California Davis, Davis, USA

    A Srinivas Reddy, Philippos K Tsourkas & Subhadip Raychaudhuri

  2. Biophysics Graduate Group, University of California Davis, Davis, USA

    Subhadip Raychaudhuri

  3. Graduate Group in Applied Mathematics, University of California Davis, Davis, USA

    Subhadip Raychaudhuri

Authors
  1. A Srinivas Reddy
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  2. Philippos K Tsourkas
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  3. Subhadip Raychaudhuri
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Correspondence to Subhadip Raychaudhuri.

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Note: Supplementary information is available on the Cellular & Molecular Immunology website.

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Srinivas Reddy, A., Tsourkas, P. & Raychaudhuri, S. Monte Carlo study of B-cell receptor clustering mediated by antigen crosslinking and directed transport. Cell Mol Immunol 8, 255–264 (2011). https://doi.org/10.1038/cmi.2011.3

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