Precursor frequencies for DNA‐specific B lymphocytes in patients with systemic lupus erythematosus (SLE)

SUMMARY 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 (<001%). 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. slgM + 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.