Search

OBJECTIVE: Regulatory interleukin-10 (IL-10)-producing B cells (B10 cells) have been shown to prevent and cure collagen-induced arthritis in mice. In humans, very little is known about B10 cells in rheumatoid arthritis (RA). Several B cell subsets, such as CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells, were suggested to be precursors of B10 cells. We aimed to analyze these B cell subsets and B10 cells in RA patients and healthy controls. METHODS: B10 cells were generated from peripheral blood mononuclear cells stimulated for 24 hours with CpG and for 4 hours with phorbol 12-myristate 13-acetate/ionomycin/brefeldin A. Intracellular B cell IL-10 was assessed by flow cytometry. Thirty-one controls and 99 RA patients were included. RESULTS: After multiple adjustments, levels of CD24(high) CD38(high) , CD24(high) CD27+, and CD5+ B cells were found to be similar in RA patients and controls. Levels of B10 cells were lower in RA patients than in controls, especially in patients with RA of \textless/=5 years' duration. Levels of B10 cells correlated inversely with the Disease Activity Score in 28 joints. This was more pronounced in patients with RA of \textless/=5 years' duration, in whom B10 cells also correlated inversely with C-reactive protein levels. Moreover, B10 cells correlated inversely with rheumatoid factor levels. CD24(high) CD38(high) and CD24(high) CD27+ B cells induced more Treg cells than did CD24(low) B cells in controls but not in RA patients. CONCLUSION: The ability of B cells to produce IL-10 was altered in RA, and this impairment influenced disease activity, biologic inflammation, and autoantibody levels, especially in patients with RA of \textless/=5 years' duration. This strongly suggests a role of B10 cells in RA initiation.

The present review on inclusion problems emphasizes papers primarily published after 1982. Materials associated with inclusions are composite materials, precipitated or transformed alloys, porous media, and polycrystals. The inclusion problems deal with the following subjects of these materials: (1) stress fields caused by non-elastic strains (eigenstrains) and; (2) stress disturbances due to heterogeneity and inhomogeneities of materials under applied stresses; (3) average elastic moduli and average thermal properties; (4) nonelastic constitutive equations; (5) behavior of inclusions including nucleation, growth, and collapse of voids; (6) cracks and inclusions including the transformation toughening, crack growth through composites and stress intensity factors; (7) sliding and debonding inclusions; and (8) dynamic effects of inclusions. The present review is an update to the review paper, which appeared in Applied Mechanics Reviews, Volume 41 (1988), and includes opinions of some of the experts who made significant contributions to the field of inclusion problems. It is our hope that we cited all the important papers relevant to the subject of inclusion problems. The first author would welcome anyone’s comments and any references which were not included in this review.