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Alterations in peripheral blood memory B cells in patients with active rheumatoid arthritis are dependent on the action of tumour necrosis factor

M Margarida Souto-Carneiro1, Vijayabhanu Mahadevan2, Kazuki Takada3, Ruth Fritsch-Stork4, Toshihiro Nanki3, Margaret Brown5, Thomas A Fleisher5, Mildred Wilson2, Raphaela Goldbach-Mansky2 and Peter E Lipsky2*

Author affiliations

1 Centro de Neurociências e Biologia Celular, Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal

2 National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA

3 Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

4 Department of Rheumatology, UMC Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands

5 Department of Laboratory Medicine, Warren Magnuson Center, NIH, 9000 Rockville Pike, Bethesda, MD 20892, USA

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Citation and License

Arthritis Research & Therapy 2009, 11:R84  doi:10.1186/ar2718

See related editorial by Leandro,

Published: 5 June 2009



Disturbances in peripheral blood memory B cell subpopulations have been observed in various autoimmune diseases, but have not been fully delineated in rheumatoid arthritis (RA). Additionally, the possible role of tumour necrosis factor (TNF) in regulating changes in specific peripheral blood memory B cell subsets in RA is still unclear.


The frequency and distribution of B cell subsets in the peripheral blood and synovial membrane of active RA patients with long-standing disease have been analysed. Additionally, the possible role of TNF in causing disturbances in memory B cell subsets in RA patients was assessed in a clinical trial with the specific TNF-neutralising antibody, infliximab.


RA patients, independent of disease duration, have a significantly lower frequency of peripheral blood pre-switch IgD+CD27+ memory B cells than healthy individuals, whereas post-switch IgD-CD27+ accumulate with increased disease duration. Notably, both pre-switch IgD+CD27+ and post-switch IgD-CD27+ memory B cells accumulate in the synovial membrane of RA patients. Finally, anti-TNF therapy increased the frequency of pre-switch IgD+CD27 memory B cells in the peripheral blood.


The data suggest that decreases in peripheral blood IgD+CD27+ pre-switch memory B cells in RA reflect their accumulation in the synovial tissue. Moreover, the significant increase in the peripheral blood pre-switch memory B cells in patients who underwent specific TNF-blockade with infliximab indicates that trafficking of memory B cells into inflamed tissue in RA patients is regulated by TNF and can be corrected by neutralising TNF.