Activated memory B cells may function as antigen-presenting cells in the joints of children with juvenile idiopathic arthritis

Arthritis Rheum. 2011 Nov;63(11):3458-66. doi: 10.1002/art.30569.

Abstract

Objective: B cells impact the perpetuation of chronic inflammatory or autoimmune diseases in multiple ways. A role of B cells as antigen-presenting cells (APCs) in the pathogenesis of chronic arthritis in humans has been suggested; however, as of yet the presence of such B cells at the site of inflammation has not been demonstrated. This study was undertaken to investigate whether synovial B cells in patients with juvenile idiopathic arthritis (JIA) might display features of APCs.

Methods: The frequency, phenotype, and immunoglobulin repertoire of synovial B cells were studied by flow cytometry and single-cell polymerase chain reaction (PCR). Cytokine expression by B cells was analyzed by real-time PCR, and interaction between B cells and T cells was investigated in a mixed lymphocyte culture.

Results: CD27+IgD- and CD27-IgD- B cells accumulated in the joints of JIA patients and displayed an activated phenotype. Both B cell subsets expressed hypermutated and class-switched immunoglobulins, indicators of memory B cells. The accumulating memory B cells expressed the costimulatory molecules CD80/CD86 and showed a higher capacity to activate allogeneic T cells and prime a Th1 phenotype than their peripheral blood counterparts.

Conclusion: Activated immunoglobulin class-switched CD27- and CD27+ memory B cells, indicating a phenotype of APCs with expression of costimulatory molecules, accumulate in the joints of patients with JIA and might be involved in the amplification of pathogenic T cell activation. These findings provide evidence that B cells play an antibody-independent immunopathologic role in human chronic inflammatory arthritis of childhood.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Arthritis, Juvenile / immunology*
  • Arthritis, Juvenile / metabolism
  • B-Lymphocyte Subsets / immunology*
  • Child
  • Child, Preschool
  • Cytokines / metabolism
  • Female
  • Humans
  • Immunologic Memory
  • Joints / immunology*
  • Male
  • Synovial Fluid / immunology
  • Synovial Fluid / metabolism
  • Synovial Membrane / immunology*
  • Synovial Membrane / metabolism

Substances

  • Cytokines