Abstract
BackgroundAutoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis.MethodsFlow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells.ResultsThe increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells.ConclusionOur study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.
Highlights
Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE)
Increased proportion of activated naïve (aNAV) and double negative 2 (DN2) B cells in lupus patients Four B cell subpopulations including switched memory (SWM; IgD-CD27+), unswitched memory (USW; IgD+CD27+), double negative (DN; IgD-CD27-), and naïve (NAV; IgD+CD27-) B cells were detected in the peripheral blood of SLE patients (Fig. 1a)
Double negative 1 (DN1) and double negative 2 (DN2) B cells were distinguished based on their expression of CXCR5, CD21, and CD11c (Fig. 2a)
Summary
Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of immunological tolerance. Recognition of self-antigens causes an abnormal autoreactive immune response resulting in B cell production of autoantibodies. The sensitive and specific biomarkers to the change of SLE disease activity will help predict the disease flares and be a useful tool for lupus care. Several cytokines (IL-6, IL-8, and IL-18) have been shown a high sensitivity with SLE disease activity [3, 4]. The identification of a biomarker that is very specific to lupus activity is needed
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