Altered blood B lymphocyte homeostasis in systemic sclerosis: Expanded naive B cells and diminished but activated memory B cells

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Abstract
Objective To determine phenotypic and functional abnormalities of blood B cell subsets in patients with systemic sclerosis (SSc). Methods Cell surface marker expression was determined by flow cytometry. Spontaneous apoptosis was evaluated by annexin V expression with flow cytometric analysis. IgG production by isolated IgD− memory B cells was examined by enzyme-linked immunosorbent assay. Results The numbers of blood CD27− naive B cells from SSc patients were increased compared with normal control cells, while memory B cells expressing medium levels of CD27 and plasmablasts expressing high levels of CD27 were reduced. In contrast, plasmablasts were the predominant population in patients with systemic lupus erythematosus (SLE). Memory B cells in SSc showed increased expression of activation markers, including CD80, CD86, and CD95, relative to normal controls. Consistent with CD95 up-regulation, SSc memory B cells exhibited augmented spontaneous apoptosis after 24-hour incubation; augmented apoptosis may explain the reduced memory B cell number. Nonetheless, isolated IgD− SSc memory B cells treated with stimuli had an enhanced ability to produce IgG. Furthermore, expression of CD19, a critical signal transduction molecule of B cells that regulates autoantibody production, was significantly increased in memory B cells as well as in naive B cells in SSc. In contrast, CD19 expression was decreased in SLE B cells. Conclusion SSc patients have distinct abnormalities of blood homeostasis and B cell compartments, characterized by expanded naive B cells and activated but diminished memory B cells. Our results suggest that CD19 overexpression in SSc memory B cells is related to their hyperreactivity.