Therapeutic implications of the anergic/postactivated status of B cells in systemic lupus erythematosus.

摘要: Systemic lupus erythematosus (SLE) is characterised by numerous abnormalities in B lineage cells, including increased CD27++ plasmablasts/plasma atypical CD27-IgD- cells with CD95, spleen tyrosine kinase (Syk)++, CXCR5- and CXCR5+ subsets anergic CD11c+Tbet+ age-associated cells. Most findings, together preclinical models, support the concept of cell hyperactivity SLE. However, it remains largely unknown whether these specific have pathogenic consequences they provide relevant therapeutic targets. Recent findings indicate a global distortion functional capability, which entire repertoire naive memory SLE exhibits an or postactivated (APA) phenotype. The APA status has some similarities to derangement T are reduced cytokine production, diminished receptor (BCR) signalling decreased Syk Bruton's phosphorylation related repeated vivo BCR stimulation as well hyporesponsiveness toll-like 9 engagement, but intact CD40 signalling. This was constitutive co-localisation CD22 linked phosphatase SHP-1 overall protein activities. Notably, co-stimulation could revert this restore signalling, downregulate transcription promote proliferation differentiation. their potential rescue bystander help conveyed through not only provides insights into possible mechanisms escape autoreactive clones from negative selection also novel ways target therapeutically.