Retention of antigen on follicular dendritic cells and B lymphocytes through complement-mediated multivalent ligand-receptor interactions: Theory and application to HIV treatment

William S. Hlavacek, Jerome K. Percus, Ora E. Percus, Alan S. Perelson, Carla Wofsy

Research output: Contribution to journalArticle

Abstract

In HIV-infected patients, large quantities of HIV are associated with follicular dendritic cells (FDCs) in lymphoid tissue. During antiretroviral therapy, most of this virus disappears after six months of treatment, suggesting that FDC-associated virus has little influence on the eventual outcome of long-term therapy. However, a recent theoretical study using a stochastic model for the interaction of HIV with FDCs indicated that some virus may be retained on FDCs for years, where it can potentially reignite infection if treatment is interrupted. In that study, an approximate expression was used to estimate the time an individual virion remains on FDCs during therapy. Here, we determine the conditions under which this approximation is valid, and we develop expressions for the time a virion spends in any bound state and for the effect of rebinding on retention. We find that rebinding, which is influenced by diffusion, may play a major role in retention of HIV on FDCs. We also consider the possibility that HIV is retained on B cells during therapy, which like FDCs also interact with HIV. We find that virus associated with B cells is unlikely to persist during therapy.

Original languageEnglish (US)
Pages (from-to)185-202
Number of pages18
JournalMathematical Biosciences
Volume176
Issue number2
DOIs
StatePublished - 2002

Keywords

  • B lymphocyte
  • Birth-death Markov chain
  • Follicular dendritic cell
  • Human immunodeficiency virus type 1
  • Immune memory
  • Multivalent ligand-receptor binding

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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