In vivo, multimodal imaging of B cell distribution and response to antibody immunotherapy in mice

Daniel L.J. Thorek, Patricia Y. Tsao, Vaishali Arora, Lanlan Zhou, Robert A. Eisenberg, Andrew Tsourkas

Research output: Contribution to journalArticle

Abstract

Background: B cell depletion immunotherapy has been successfully employed to treat non-Hodgkin's lymphoma. In recent years, increasing attention has been directed towards also using B-cell depletion therapy as a treatment option in autoimmune disorders. However, it appears that the further development of these approaches will depend on a methodology to determine the relation of B-cell depletion to clinical response and how individual patients should be dosed. Thus far, patients have generally been followed by quantification of peripheral blood B cells, but it is not apparent that this measurement accurately reflects systemic B cell dynamics. Methodology/Principal Findings: Cellular imaging of the targeted population in vivo may provide significant insight towards effective therapy and a greater understanding of underlying disease mechanics. Superparamagnetic iron oxide (SPIO) nanoparticles in concert with near infrared (NIR) fluorescent dyes were used to label and track primary C57BL/6 B cells. Following antibody mediated B cell depletion (anti-CD79), NIR-only labeled cells were expeditiously cleared from the circulation and spleen. Interestingly, B cells labeled with both SPIO and NIR were not depleted in the spleen. Conclusions/Significance: Whole body fluorescent tracking of B cells enabled noninvasive, longitudinal imaging of both the distribution and subsequent depletion of B lymphocytes in the spleen. Quantification of depletion revealed a greater than 40% decrease in splenic fluorescent signal-to-background ratio in antibody treated versus control mice. These data suggest that in vivo imaging can be used to follow B cell dynamics, but that the labeling method will need to be carefully chosen. SPIO labeling for tracking purposes, generally thought to be benign, appears to interfere with B cell functions and requires further examination.

Original languageEnglish (US)
Article numbere10655
JournalPloS one
Volume5
Issue number5
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Thorek, D. L. J., Tsao, P. Y., Arora, V., Zhou, L., Eisenberg, R. A., & Tsourkas, A. (2010). In vivo, multimodal imaging of B cell distribution and response to antibody immunotherapy in mice. PloS one, 5(5), [e10655]. https://doi.org/10.1371/journal.pone.0010655