Abstract
The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis.
Highlights
Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by an excessive deposition of extracellular matrix on skin and internal organs, vasculopathy, and the presence of a wide spectrum of autoantibodies
Altered Frequencies of B-Cell Subpopulations in Peripheral Blood of Systemic Sclerosis Patients To investigate whether the frequency of different B-cell subpopulations is altered in peripheral blood of SSc patients, we analyzed them by flow cytometry
Since the relative frequency of memory B cells was dramatically decreased within SSc patients’ B cells, the observed increase in the percentage of total B cells can be explained by an expansion of naive B cells
Summary
Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by an excessive deposition of extracellular matrix on skin and internal organs, vasculopathy, and the presence of a wide spectrum of autoantibodies. This disease is classified into limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) according to the degree of skin sclerosis, the presence of interstitial lung disease or pulmonary arterial hypertension, and the autoantibody profile [1]. CD19 strengthens signals generated by the B-cell antigen receptor (BCR) and by CD40, which is activated by CD40 ligand (CD40L)-expressing T cells [8,9,10]. Another complement receptor that is expressed on B cells – CD35 (CR1) – has been proposed to deliver inhibitory signals, opposing CD21 signals in the regulation of B-cell activation [11]
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