Precursor frequencies for DNA-specific B lymphocytes in patients with systemic lupus erythematosus (SLE).
Precursor frequencies for anti-DNA-secreting B cells were estimated in six healthy donors and 18 SLE patients with active and inactive disease. Precursors for IgG anti-dsDNA-secreting B cells were exclusively detected in SLE patients (73% of active patients and one inactive patient, 0.01-0.99% of IgG-producing B cells). These frequencies were in the same order of magnitude as frequencies of precursors for IgG anti-tetanus toxoid, which were detectable in three healthy volunteers after booster vaccination (0.07-0.8% of IgG-producing B cells), but not before (< 0.01%). Precursors for IgG anti-ss-DNA secreting B cells were observed in 33% of healthy donors and in 78% of SLE patients (0.01-0.32% of IgG-producing B cells). Only patient-derived IgG anti-DNA clones cross-reacted with (33%) or were monoreactive to dsDNA (12%). Precursors for IgM anti-DNA-secreting B cells were observed in healthy donors and SLE patients in comparable frequencies and with similar reactivities with ssDNA and dsDNA. Segregation analyses and sorting experiments showed that > 94% of clones secreting IgG anti-DNA were derived from in vivo sIgG+ B cells. sIgM+ B cells were induced to switch in vitro; however, only twice were cultures containing IgM and IgG anti-DNA antibodies observed under clonal conditions. In conclusion, our results indicate that precursor B cells for IgG anti-dsDNA in SLE patients are similarly selected and expanded as are precursor B cells specific for foreign antigens such as tetanus toxoid.
Schwab
J
J
Clinical Research Unit on Rheumatology, Albert-Ludwigs-University, Freiburg, Germany.
Lukowsky
A
A
Volk
H D
HD
Peter
H H
HH
Melchers
I
I
D000328:Adult; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000918:Antibody Specificity; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013745:Tetanus Toxoid / Q000276:immunology
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D013745:Tetanus Toxoid; D004247:DNA