Aberrant Lower CD6 Expression on Peripheral B Cells Associated With Liver/Kidney Injury and Autoantibody Production of Systemic Lupus Erythematosus Patients

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease characterised by aberrant activation and differentiation of autoreactive T and B cells, as well as the overproduction of autoantibodies. CD6, a cell-surface glycoprotein, regulates lymphocyte activation, differentiation and survival, and is implicated in the pathogenesis of various autoimmune disorders. In SLE, the CD6/activated leukocyte cell adhesion molecule (ALCAM) pathway promotes renal T-cell immune responses. However, the distribution, expression, and function of CD6 in lupus B cells remain poorly understood. In this work, we employed flow cytometry and multi-colour immunohistochemical staining to analyse the expression and distribution of CD6 on peripheral B cells. Correlation analysis was performed to assess the associations of CD6 and clinical indicators of disease severity. We found that SLE patients exhibited significantly reduced CD6 expression on peripheral CD19+ B, CD19+CD27- B, CD19+CD27+ B, naïve B, CD19+CD27-IgD- double-negative B (DNB) and CD19+CD27+IgD+ B cells. Moreover, CD6 expression was negatively correlated with serum levels of alanine transaminase (ALT), lactate dehydrogenase (LDH) and the degree of white blood cell (WBC) depletion. Notably, SLE patients positive for antinuclear antibody (ANA) or anti-SSA antibody displayed lower CD6 expression on circulating B cells. Additionally, CD6 expression in B cells was predominantly localised in the extrafollicular (EF) region of human tonsils, suggesting a potential regulatory role of CD6 in EF B-cell responses. In conclusion, dysregulated CD6 expression on peripheral B cells might be related to liver/kidney injury and ANA/anti-SSA antibody production in SLE patients.