Phenotypic and functional characterization of switch memory B cells from patients with oligoarticular juvenile idiopathic arthritis
- Equal contributors
1 Laboratory of Oncology, IRCCS G. Gaslini, Largo G. Gaslini 5, Genoa, 16148, Italy
2 Second Division of Pediatrics, IRCCS G. Gaslini, Largo G. Gaslini 5, Genoa, 16148, Italy
3 University of Genoa, Viale Benedetto XV, Genoa, 16100, Italy
4 Human Anatomy Section, IRCCS G. Gaslini, Largo G. Gaslini 5, Genoa, 16148, Italy
5 Clinical Epidemiology and Biostatistics Unit, Scientific Direction, IRCCS G. Gaslini Institute, Largo G. Gaslini 5, Genoa, 16148, Italy
6 IRCCS G. Gaslini, Largo G. Gaslini 5, Genoa, 16148, Italy
Arthritis Research & Therapy 2009, 11:R150 doi:10.1186/ar2824Published: 5 October 2009
In chronic inflammatory disorders, B cells can contribute to tissue damage by autoantibody production and antigen presentation to T cells. Here, we have characterized synovial fluid and tissue B-cell subsets in patients with oligoarticular juvenile idiopathic arthritis (JIA), an issue not addressed before in detail.
B cells from synovial fluid (SF) and peripheral blood (PB) of 25 JIA patients, as well as from PB of 20 controls of comparable age, were characterized by multicolor flow cytometry. Immunoglobulin-secreting cells were detected by ELISPOT. Immunohistochemical analyses of synovial tissue from three JIA patients were performed.
JIA SF B cells were enriched in CD27+ and CD27- switch memory B cells, but not in CD27+ IgM memory B cells, compared with patient and control PB. Plasma blasts were more abundant in SF and secreted higher amounts of IgG. Lymphoid aggregates not organized in follicle-like structures were detected in synovial tissue sections and were surrounded by CD138+ plasma cells. Finally, transitional B cells were significantly increased in JIA PB versus SF or control PB. CCR5, CCR8, CXCR2, and CXCR3 were upregulated, whereas CCR6, CCR7, and CXCR5 were downregulated on SF CD27+ and CD27- switch memory B cells compared with their circulating counterparts. SF CD27+ and CD27- switch memory B cells expressed at high levels the costimulatory molecule CD86 and the activation marker CD69.
This study demonstrates for the first time an expansion of activated switch memory B cells and of IgG-secreting plasma blasts in the SF from oligoarticular JIA patients. Memory B cells belonged to either the CD27+or the CD27- subsets and expressed CD86, suggesting their involvement in antigen presentation to T cells. Patterns of chemokines-receptor expression on CD27+ and CD27- switch memory B cells delineated potential mechanisms for their recruitment to the inflamed joints.