Abstract
Systemic lupus erythematosus (SLE) is a generalized autoimmune disease characterized by abnormal B cell activation and the occurrence of increased frequencies of circulating plasma cells (PC). The molecular characteristics and nature of circulating PC and B cells in SLE have not been completely characterized. Microarray analysis of gene expression was used to characterize circulating PC in subjects with active SLE. Flow cytometry was used to sort PC and comparator B cell populations from active SLE blood, normal blood and normal tonsil. The gene expression profiles of the sorted B cell populations were then compared.SLE PC exhibited a similar gene expression signature as tonsil PC. The differences in gene expression between SLE PC and normal tonsil PC and tonsil plasmablasts (PB) suggest a mature Ig secreting cell phenotype in the former population. Despite this, SLE PC differed in expression of about half the genes from previously published gene expression profiles of normal bone marrow PC, indicating that these cells had not achieved a fully mature status. Abnormal expression of several genes, including CXCR4 and S1P1, suggests a mechanism for the persistence of SLE PC in the circulation. All SLE B cell populations revealed an interferon (IFN) gene signature previously only reported in unseparated SLE peripheral blood mononuclear cells. These data indicate that SLE PC are a unique population of Ig secreting cells with a gene expression profile indicative of a mature, but not fully differentiated phenotype.
Highlights
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by clinical and pathologic heterogeneity
Peripheral Blood and Tonsil Populations Tonsil B cell populations were obtained from young patients undergoing routine tonsillectomy with the use of a IRB protocol approved by the Clinical Center at the National Institutes of Health (Bethesda, MD) in accordance with the precepts established by the Declaration of Helsinki
Molecular Characterization of Ig Secreting Cells To verify the molecular characteristics of tonsil PB and plasma cells (PC), we first performed gene expression profiling of tonsillar B cell populations
Summary
SLE is a chronic autoimmune disease characterized by clinical and pathologic heterogeneity. The B cell abnormalities include an increase in the number of circulating plasma cells (PC), disturbances in memory and naıve subsets, an activated phenotype and poor in vitro stimulation and survival [3]. The frequency of circulating PC correlates with disease activity, as measured by the SLEDAI scoring system, and the production of autoantibodies [4]. The appearance of increased numbers of PC in the circulation of subjects with active SLE appears to reflect increased production in germinal centers, since circulating SLE PC contain highly mutated immunoglobulin (Ig) genes and their presence rapidly decreases following administration of a blocking monoclonal antibody to CD154 that limits T cell-B cell collaboration and germinal center formation [6]. The phenotypic markers of circulating SLE PC are CD27++CD38++CD19loCD138+IgD2IgG+ [1,6,7]
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