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

Abstract

SUMMARYPrecursor 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 (007-0 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 (0-01-032% 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.

Oxidized Hemoglobin Is Antigenic and Immunogenic in Lupus

“…The fact that the non-specific inflammatory stimulus that LPS delivers did not elicit such discriminatory responses argues for an Hb-specific effect. The second correlate was the higher anti-Hb antibody-secreting B cell precursor frequencies observed in lupus-prone mice, mimicking the higher frequencies of anti-dsDNA, anti-Sm, anti-Ro, and anti-La antibody-secreting B cells seen in lupus in previous studies ( 28 – 30 ), an observation supporting the positioning of Hb as a bona fide autoantigen. The third correlate was the age-related increase in anti-Hb antibodies in NZM mice; incidence rates of reactivity were much higher in these mice than in SLE patients, possibly on account of genetic identity of the former, since immune responses are influenced by genes encoded by the major histocompatibility complex.…”

Peripheral B cell abnormalities and disease activity in systemic lupus erythematosus

“…1,2 The reason for hyperactivated B cells is largely unknown, especially whether it is intrinsic or extrinsic (Table 1). Spontaneous Ig production by peripheral blood lymphocytes ex vivo has been documented in SLE patients previously 3,4 and distinct abnormalities of peripheral B cell homeostasis in SLE patients have been reported. [5][6][7][8] Interestingly, absolute B cell numbers and memory B cells in SLE are reduced, whereas transitional B cells or plasmablasts are expanded in the peripheral blood of lupus patients.…”