In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells

Am J Transplant. 2012 Feb;12(2):341-50. doi: 10.1111/j.1600-6143.2011.03833.x. Epub 2011 Nov 9.

Abstract

Rituximab is a chimeric anti-CD20 monoclonal antibody (mAb) used in B-cell malignancies, various autoimmune disorders and organ transplantation. Although administration of a single dose of rituximab results in full B-cell depletion in peripheral blood, there remains a residual B-cell population in secondary lymphoid organs. These nondepleted B cells might be altered by exposure to rituximab with subsequent immunomodulatory effects. Therefore, we analyzed in vitro the effects of rituximab on proliferation, activation and differentiation of CD19(+) B cells by means of carboxyfluorescein succinimidyl ester (CFSE)-based multiparameter flow cytometry. Rituximab inhibited the proliferation of CD27(-) naïve, but not of CD27(+) memory B cells. Interestingly, upon stimulation with anti-CD40 mAb and interleukin-21 in the presence of rituximab there was an enrichment of B cells that underwent only one or two cell divisions and displayed an activated naïve phenotype (CD27(-)IgD(+)CD38(-/+)). The potency of prestimulated B cells to induce T-cell proliferation was increased by exposure of the B cells to rituximab. Of note, after stimulation with rituximab-treated B cells, proliferated T cells displayed a more Th2-like phenotype. Overall, these results demonstrate that rituximab can affect human B-cell phenotype and function, resulting in an altered outcome of B-T cell interaction.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Antigens, CD20
  • B-Lymphocytes / cytology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Flow Cytometry
  • Humans
  • Immunologic Factors / pharmacology
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Phenotype
  • Rituximab

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Immunologic Factors
  • Rituximab