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-α (IFN-α) 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, IFIT1, 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.


CONCLUSIONS
The findings suggest that elevated BAFF expression supports expansion of the T2 B cell compartment and contributes to a breach in tolerance in patients with SLE.
Arthritis Centre of Excellence, Division of Genetics and Development, and the Division of Health Care and Outcomes Research, Toronto Western Hospital Research Institute, University Health Network, Toronto, Ontario, Canada.
Carolina
C
Landolt-Marticorena
Robert
R
Wither
Heather
H
Reich
Andrew
A
Herzenberg
James
J
Scholey
Dafna D
DD
Gladman
Murray B
MB
Urowitz
Paul R
PR
Fortin
Joan
J
Wither
D000293:Adolescent; D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000503:physiopathology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008875:Middle Aged; D010641:Phenotype; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
D053264:B-Cell Activating Factor; D016898:Interferon-alpha