IL-6 Modulates CD5 Expression in B Cells from Patients with Lupus by Regulating DNA Methylation

摘要: B lymphocytes from patients with systemic lupus erythematosus (SLE) are characterized by reduced expression levels of membrane CD5. Recent studies our laboratory have revealed that the level CD5 is determined relative two alternative isoforms; CD5-E1A, which expressed on membrane, and CD5-E1B, retained in cytoplasm. Using bisulfite sequencing methylation-sensitive endonuclease assays we show promoter for CD5-E1B isoform demethylated cells SLE but not healthy controls. We go to differential methylation more pronounced following BCR engagement. As a result this demethylation, mRNA transcribed at expense CD5-E1A transcription. provide further evidence production high IL-6 abrogates ability induce DNA methyl transferase (DNMT1) then methylate DNA, an effect reversed presence blocking Ab receptor. The pattern demethylation CpG islands similar those controls stimulated IL-6, or treated inhibitor PD98059. study reveals engagement constitutive down-regulates CD5, negatively regulates signaling, cells. This altered signaling could, turn, promote activation expansion autoreactive patients.