PRECURSOR FREQUENCIES FOR DNA-SPECIFIC B-LYMPHOCYTES IN PATIENTS WITHSYSTEMIC 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 disea se. Precursors for IgG anti-dsDNA-secreting B cells were exclusively d etected in SLE patients (73% of active patients and one inactive patie nt, 0.01-0 .99% of IgG-producing B cells). These frequencies were in t he same order of magnitude as frequencies of precursors for IgG anti-t etanus toroid, which were detectable in three healthy volunteers after booster vaccination (0.07-0.8% of IgG-producing B cells), but not bef ore (< 0.01%). Precursors for IgG anti-ss-DNA secreting B cells were o bserved 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%). Precurso rs for IgM anti-DNA-secreting B cells were observed in healthy donors and SLE patients in comparable frequencies and with similar reactiviti es with ssDNA and dsDNA. Segregation analyses and sorting experiments showed that > 94% of clones secreting IgG anti-DNA were derived from i n vivo sIgG(+) B cells. sIgM(+) B cells were induced to switch in vitr o; however, only twice were cultures containing IgM and IgG anti-DNA a ntibodies observed under clonal conditions. In conclusion, our results indicate that precursor B cells for IgG anti-dsDNA in SLE patients ar e similarly selected and expanded as are precursor B cells specific fo r foreign antigens such as tetanus toroid.