Background and objectives B lymphocytes have the capacity to modulate autoimmune and inflammatory responses. In mice, activation of dendritic cells (DCs) and Th1 differentiation of T lymphocytes are repressed by a B cell dependent regulation. The aim of our study was to further analyse the regulatory properties of human B cells in systemic lupus erythematosus (SLE).
Materials and methods B cells purified from the peripheral blood (PB) of four SLE patients and six healthy controls (HCs) were stimulated through CD40 and TLR9. They were co-cultured with either autologous DCs that were preliminary differentiated from PB monocytes with GM-CSF plus IL-4 and then with LPS plus interferon γ, or with autologous T cells stained with CFSE and stimulated with anti-CD3 and anti-CD28 antibodies. All analyses were performed by flow cytometry. Variations of HLA-DR, CD80 and CD86 expressions and of IL-12 production by the DCs were used to examine the B cell effects on DCs. The modulation of CFSE fluorescence was evaluated to determine the B cell effect on the T cell proliferative response.
Results When cultured alone, differentiated DCs from HCs and SLE patients strongly expressed HLA-DR, CD80 and CD86, and produced high level of IL-12. In the presence of autologous B cells, densities of HLA-DR, CD80 and CD86 were decreased, while the production of IL-12 was downregulated in HC co-cultures, but not in SLE co-cultures. T lymphocytes from HCs and SLE patients proliferated following anti-CD3 and anti-CD28 stimulation. In the presence of autologous B cells, the proliferative response was inhibited in HC co-cultures, but unaffected in SLE co-cultures.
Conclusions First, we demonstrate that human B cells can regulate DC differentiation. This is partially impaired in SLE since IL-12 production is not suppressed with SLE B cells. Second, human B cells can also control the proliferation of T cells. This capacity is defective in patients with SLE, since their B cells do not prevent T cell proliferation. This data raises the issue as to how overcome each deficiency in order to recover efficient regulatory B cell functions.
Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.