Presence of a population of CD20+, CD38- B lymphocytes with defective proliferative responsiveness in the synovial compartment of patients with rheumatoid arthritis

Arthritis Rheum. 2001 Sep;44(9):2029-37. doi: 10.1002/1529-0131(200109)44:9<2029::AID-ART352>3.0.CO;2-2.


Objective: To provide a comprehensive understanding of the humoral immune response that takes place at the site of inflammation in rheumatoid arthritis (RA), we studied the functional properties of synovial B cells. In particular, the response to various modes of mitogen stimulation was investigated.

Methods: Purified synovial fluid (SF) B cells were cultured in the presence of CD40 ligand (CD40L)-expressing fibroblasts and cytokines, activated T cells, or phorbol myristate acetate (PMA)/ionomycin. Proliferation was determined by 3H-thymidine incorporation. Release of intracellular calcium was studied by flow cytometry.

Results: The inflamed joints of RA patients contained a population of CD20+,CD38- B cells with dramatically impaired mitogen responsiveness. Although the Ig-producing capacity was intact, these cells failed to proliferate in response to (a) CD40 in the presence of interleukin-2 (IL-2) and IL-10, (b) activated T cells, or (c) stimulation via the B cell receptor. Moreover, SF CD20+,CD38- B cells revealed a defective B cell receptor-induced Ca2+ influx, reminiscent of anergic B cells. Release of intracellular Ca2+ by ionomycin in the presence of the protein kinase C activator PMA did not restore the proliferative capacity. These findings indicate blockades in the proximal and distal intermediates involved in mitogen signaling.

Conclusion: SF CD20+,CD38- B cells have functionally impaired proliferative responsiveness. The capacity of these cells to respond to activation by the production of Ig supports the notion that these cells might serve as Ig-producing effector cells and, as such, play a role in the pathophysiology of RA.

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Adult
  • Aged
  • Antigens, CD*
  • Antigens, CD20 / analysis*
  • Antigens, Differentiation / analysis*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • B-Lymphocytes / chemistry
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD40 Antigens / immunology
  • CD40 Ligand / pharmacology
  • Calcium Signaling / immunology
  • Carcinogens / pharmacology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cells, Cultured
  • Female
  • Humans
  • Immunoglobulins / biosynthesis
  • Interleukin-10 / pharmacology
  • Interleukin-2 / pharmacology
  • Ionomycin / pharmacology
  • Ionophores / pharmacology
  • Male
  • Membrane Glycoproteins
  • Middle Aged
  • NAD+ Nucleosidase / analysis*
  • Oxidation-Reduction
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • Synovial Membrane / immunology*
  • Synovial Membrane / pathology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • Tetradecanoylphorbol Acetate / pharmacology


  • Antigens, CD
  • Antigens, CD20
  • Antigens, Differentiation
  • CD40 Antigens
  • Carcinogens
  • Immunoglobulins
  • Interleukin-2
  • Ionophores
  • Membrane Glycoproteins
  • Interleukin-10
  • CD40 Ligand
  • Ionomycin
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1
  • Tetradecanoylphorbol Acetate