Rituximab-mediated depletion of cynomolgus monkey B cells in vitro in different matrices: possible inhibitory effect of IgG

Int Immunopharmacol. 2004 Aug;4(8):1117-24. doi: 10.1016/j.intimp.2004.04.015.

Abstract

The mechanism of rituximab-mediated depletion of nonmalignant CD20+B cells remains to be clarified. In this report, we examine contributions of complement- and cell-dependent killing to the rituximab-mediated depletion of cynomolgus monkey B cells in the in vitro assay. B cell depletion was assessed in whole blood, buffer, autologus plasma (plasma), heat-inactivated plasma (H/I plasma), and cobra venom factor (CVF)-treated plasma matrices in cynomolgus monkey and human samples. Rituximab-mediated B cell depletion in buffer appeared to be greater than that in whole blood or in autologus plasma. Heat inactivation of plasma resulted in the degree of B cell depletion closer to that seen in buffer, whereas CVF treatment of plasma had no effect on B cell depletion. Addition of IgG to the buffer decreased the degree of B cell depletion. The results of these studies imply that (i) plasma components (including complement) are not the mediators of the rituximab-triggered B cell depletion in the in vitro assay, suggesting that cell-mediated mechanisms are likely to be responsible for in vitro killing of normal B cells, and that (ii) some plasma components appear to inhibit rituximab-mediated B cell depletion in the in vitro assay, with IgG identified as a possible inhibitor component.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 / metabolism
  • Antineoplastic Agents / pharmacology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects*
  • Buffers
  • Complement C1q / physiology
  • Elapid Venoms / pharmacology
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / physiology*
  • In Vitro Techniques
  • Macaca fascicularis
  • Rituximab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Antineoplastic Agents
  • Buffers
  • Elapid Venoms
  • Immunoglobulin G
  • cobra venom factor
  • Rituximab
  • Complement C1q