Decreased frequency and activated phenotype of blood CD27 IgD IgM B lymphocytes is a permanent abnormality in systemic lupus erythematosus patients.
BACKGROUND
Systemic lupus erythematosus (SLE) is characterized by B cell hyper-activation and auto-reactivity resulting in pathogenic auto-antibody generation. The phenotypic analysis of blood B cell subsets can be used to understand these alterations.


METHODS
The combined detection of CD19, CD27 and IgD (or IgM) by flow cytometry (FC) analysis delineates five well-defined blood B cell-subsets: naive, switched (S) memory, double negative (DN) memory and CD27 IgD IgM (non-switched memory) B lymphocytes, and plasma cells (PCs). This phenotypic study was performed in 69 consecutive SLE patients and 31 healthy controls.


RESULTS
SLE patients exhibited several abnormalities in the distribution of these B cell subsets, including elevated levels of DN memory B cells and PCs, and decreased CD27 IgD IgM B cells. Active SLE patients also showed decreased presence of S memory B cells and increased proportions of naive B lymphocytes. Nevertheless, when the patients in remission who did not require treatment were studied separately, the only remaining abnormality was a reduction of the CD27 IgD IgM B cell-subset detectable in most of these patients. The level of reduction of CD27 IgD IgM B cells was associated with elevated values of serum SLE auto-antibodies. Further analysis of this latter B cell-subset specifically showed increased expression of CD80, CD86, CD95, 9G4 idiotype and functional CXCR3 and CXCR4.


CONCLUSIONS
The presence of a reduced blood CD27 IgD IgM B cell-subset, exhibiting an activated state and enriched for auto-reactivity, is a consistent B cell abnormality in SLE. These findings suggest that CD27 IgD IgM B lymphocytes play a role in the pathogenesis of this disease.
Rodríguez-Bayona
Beatriz
B
Unidad de Investigación, Hospital Universitario Puerta del Mar, Avenida Ana de Viya 21, 11009 Cádiz, Spain.
Ramos-Amaya
Ana
A
Pérez-Venegas
José J
JJ
Rodríguez
Carmen
C
Brieva
José A
JA
D000328:Adult; D000368:Aged; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002452:Cell Count; D002465:Cell Movement; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*
D007072:Immunoglobulin D; D007075:Immunoglobulin M; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7