Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
B Cell Depletion Enhances T Regulatory Activity Essential in the Suppression of Arthritis.
Ashaye, Susan, Hamel, Keith, Cao, Yanxia, Wang, Yumei, Glant, Tibor T., Finnegan, Alison
B cell depletion is an effective therapy in Rheumatoid arthritis (RA), however, the mechanism responsible for suppression of disease is not clear. Autoantibodies are decreased in B cell depleted patients but the decrease does not necessarily correlate with clinical outcome suggesting that other mechanism may be effective. In a previous reported, we showed that in a murine model of arthritis proteoglycan-induced arthritis (PGIA) that B cell depletion inhibits autoreactive T cell responses. Recent studies of B cell depletion therapy also indicate a role for B cells in suppressing regulatory mechanisms. Here we tested where B cells inhibited both the expansion and the function of T regulatory (Treg) cells in PGIA.
B cells were depleted using in mice with PGIA an anti-CD20 mAb and Treg cell determined by Treg phenotype as CD4+ CD25+ Foxp3+ by flow cytometry. T cell responses were measured by T cell proliferation and cytokine secretion.
Treg cell percentages were elevated in B cell-depleted mice in comparison to control Ab treated. CD4+CD25+ cells from B cell depleted mice expressed increased amounts of Foxp3 and were significantly more suppressive than those from control Ab-treated mice. The depletion of Treg cells with an anti-CD25 mAb concurrent with B cell depletion therapy restored the severity of PGIA to levels equal to untreated mice. CD4+ T cell recall responses to the immunizing antigen returned as measured by T proliferation and cytokine production.
These studies demonstrate B cells contribute to inflammation by inhibiting Treg cell expansion and function. B cell may inhibit T reg cells directly or indirectly by promoting preferential differentiation of naïve CD4+ T cells towards a proinflammatory effector phenotypes rather than Tregs. Alternatively, the B cells act as APCs may expand the pool of autoreactive Teffs beyond the control of a Treg response. Further elucidation of the mechanisms utilized by B cells to suppress Tregs will have a major impact on the development of new therapies for the treatment of diseases.
To cite this abstract, please use the following information:
Ashaye, Susan, Hamel, Keith, Cao, Yanxia, Wang, Yumei, Glant, Tibor T., Finnegan, Alison; B Cell Depletion Enhances T Regulatory Activity Essential in the Suppression of Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1760