Increased Expression of B Cell Activation Factor Supports the Abnormal Expansion of Transitional B Cells in Systemic Lupus Erythematosus

Objective. To examine the relationship between interferon-alpha (IFN-alpha) and dysregulation of B cell activation factor (BAFF) and specific B cell phenotypes in systemic lupus erythematosus (SLE). Methods. Four-color flow cytometry was used to examine the peripheral B cell populations in patients with SLE. RNA was isolated from the peripheral blood of 87 patients and BAFF expression was determined by quantitative polymerase chain reaction (PCR) and normalized to GAPDH. The expression levels of 5 IFN-responsive genes (LY6E, OAS1, IFITI, ISG15, and MX1) were determined by quantitative PCR and totaled to generate a global IFN score. The correlations were examined between peripheral B cell populations (including transitional, pregerminal, plasmablasts, and memory) and the expression of BAFF and the global IFN score. Results. Examination of the peripheral B cell populations in SLE demonstrated a relative expansion of the transitional B cell and plasmablast compartment and a reduction in the memory B cell population. Expressions of BAFF and global IFN score were elevated in patients with SLE compared to healthy controls. A strong positive correlation was noted between BAFF expression and the relative proportion of late transitional (T2) B cells. The proportions of more mature B cell phenotypes did not correlate with BAFF expression. The global IFN score was strongly associated with the level of BAFF expression and moderately correlated with the proportion of late transitional B cells. Conclusion. The findings suggest that elevated BAIT expression supports expansion of the T2 B cell compartment and contributes to a breach in tolerance in patients with SLE. (First Release Jan 15 2011; J Rheumatol 2011;38:642-51; doi:10.3899/jrheum.100214)