Expression of recombination activating genes 1 and 2 in peripheral B cells of patients with systemic lupus erythematosus.
OBJECTIVE
To analyze immunoregulatory abnormalities in patients with systemic lupus erythematosus (SLE) by assessing the expression of messenger RNA (mRNA) for types 1 and 2 recombination activating genes (RAG) in the peripheral blood of patients with active SLE.


METHODS
We examined B cell populations and also individual B cells from patients with SLE for the expression of RAG mRNA.


RESULTS
Analysis of bulk mRNA indicated that RAG1 and RAG2 mRNA were found routinely in peripheral B cells of patients with active SLE, but not in healthy subjects. When assessed on a single-cell basis, there was a 3-fold increase in the frequency of RAG1- and RAG2-expressing B cells in SLE patients compared with healthy subjects. Notably, B cells expressing both RAG1 and RAG2 mRNA expressed only IgD mRNA, but not IgG mRNA. Fifty percent of RAG-expressing B cells also expressed VpreB mRNA, whereas all expressed CD154 mRNA. Phenotypic analysis indicated that RAG-expressing B cells were activated, mature B cells.


CONCLUSIONS
These results indicate that RAG expression is up-regulated in peripheral IgD+ and VpreB+ B cells of patients with active SLE. These cells may contribute to the immunoregulatory abnormalities in patients with SLE.
University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hermann J
HJ
Girschick
Amrie C
AC
Grammer
Toshihiro
T
Nanki
Eduardo
E
Vazquez
Peter E
PE
Lipsky
D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000737:chemistry / Q000502:physiology*; D023201:CD40 Ligand / Q000235:genetics; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000276:immunology; D016654:Genes, RAG-1 / Q000235:genetics*; D006801:Humans; D007072:Immunoglobulin D / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D007156:Immunologic Memory / Q000502:physiology; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics; D009687:Nuclear Proteins; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation / Q000276:immunology
D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007146:Immunoglobulin lambda-Chains; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; C064655:V(D)J recombination activating protein 2; D023201:CD40 Ligand; D004253:DNA Nucleotidylexotransferase