Rituximab therapy reduces activated B cells in both the peripheral blood and bone marrow of patients with rheumatoid arthritis: depletion of memory B cells correlates with clinical response

Arthritis Res Ther. 2009;11(4):R131. doi: 10.1186/ar2798. Epub 2009 Aug 28.


Introduction: Bone marrow (BM) is an immunologically privileged site where activated autoantibody-producing B cells may survive for prolonged periods. We investigated the effect of rituximab (anti-CD20 mAb) in peripheral blood (PB) and BM B-cell and T-cell populations in active rheumatoid arthritis (RA) patients.

Methods: Active RA patients received rituximab (1,000 mg) on days 1 and 15. PB (n = 11) and BM (n = 8) aspirates were collected at baseline and at 3 months. We assessed B-cell and T-cell populations using triple-color flow cytometry.

Results: Rituximab therapy decreased PB (from a mean 2% to 0.9%, P = 0.022) but not BM (from 4.6% to 3.8%, P = 0.273) CD19+ B cells, associated with a significant reduction in the activated CD19+HLA-DR+ subset both in PB (from 55% to 19%, P = 0.007) and in BM (from 68% to 19%, P = 0.007). Response to rituximab was preceded by a significant decrease in PB and BM CD19+CD27+ memory B cells (P = 0.022). These effects were specific to rituximab since anti-TNF therapy did not reduce total or activated B cells. Rituximab therapy did not alter the number of activated CD4+HLA-DR+ and CD4+CD25+ T cells.

Conclusions: Rituximab therapy preferentially depletes activated CD19+HLA-DR+ B cells in the PB and BM of active RA patients. Clinical response to rituximab is associated with depletion of CD19+CD27+ memory B cells in PB and BM of RA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19 / immunology
  • Antigens, CD19 / metabolism
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Bone Marrow Cells / drug effects*
  • Female
  • Flow Cytometry
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunologic Memory / drug effects*
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Rituximab
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19
  • Antirheumatic Agents
  • HLA-DR Antigens
  • Rituximab