Open AccessPresence of a population of CD20+,CD38− B lymphocytes with defective proliferative responsiveness in the synovial compartment of patients with rheumatoid arthritis
Author(s) -
ReparonSchuijt Carelle C.,
Van Esch Wim J. E.,
Van Kooten Cees,
Ezendam Nicole P. M.,
Levarht Eleonora W. N.,
Breedveld Ferdinand C.,
Verweij Cornelis L.
Publication year - 2001
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(200109)44:9<2029::aid-art352>3.0.co;2-2
Subject(s) - cd40 , ionomycin , cd38 , synovial membrane , immunology , population , b cell , t cell , biology , microbiology and biotechnology , immune system , chemistry , intracellular , medicine , cytotoxic t cell , inflammation , antibody , biochemistry , stem cell , in vitro , environmental health , cd34
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 3 H‐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 Ca 2+ influx, reminiscent of anergic B cells. Release of intracellular Ca 2+ 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.