Xw. He et al., INCREASED RESPONSIVENESS OF RHEUMATOID FACTOR-PRODUCING B-CELLS IN SERONEGATIVE AND SEROPOSITIIVE RHEUMATOID-ARTHRITIS, Arthritis and rheumatism, 39(9), 1996, pp. 1499-1506
Objective. To compare the frequencies and responsiveness of rheumatoid
factor (RF)-producing B cells in the peripheral blood of patients wit
h seronegative and seropositive rheumatoid arthritis (RA). Methods. Fr
equencies of IgM+, IgG+, and RF+ B cells were determined by limiting-d
ilution analysis of purified peripheral blood B cells from 6 patients
with seropositive RA, 8 patients with seronegative RA, and 7 normal co
ntrols. B cell help was provided by cloned T helper cells, which were
stimulated by either anti-CD3 or the bacterial superantigen staphyloco
ccal enterotoxin D (SED). IgM and IgG antibodies and RF in culture sup
ernatants were detected by enzyme-linked immunosorbent assay. Results.
In the presence of anti-CD3-stimulated T helper cells, 2-10% of B cel
ls from normal individuals secreted IgM and IgG antibodies. The freque
ncy of RF+ B cells was low and ranged from 1:182 to 1:885 (RF+: IgM+)
B cells. In patients with seropositive RA, the numbers of Ig-producing
B cells were reduced by a factor of 2, while the fraction of RF+ B ce
ll precursors was expanded by more than 50-fold (7-20% of IgM+ B cells
; P = 0.004). Patients with seronegative RA had higher frequencies of
RF-producing B cells (1.5-6% of IgM+ B cells) than normal individuals
(P = 0.002), but not to the same extent as seropositive patients (P =
0.002). Stimulation of B cells using SED preferentially induced RF+ B
cells in normal controls and in patients with seronegative and seropos
itive RA. Conclusion. B cell precursors with the potential to secrete
RF were detectable in high frequencies in normal individuals and in pa
tients with seropositive and seronegative RA. In all donors, these B c
ells could be stimulated with the bacterial superantigen SED. In norma
l individuals, RF+ B cells remained nonresponsive to help provided by
anti-CD3-activated T cells, but were responsive in RA patients. Serone
gative and seropositive RA form a continuous spectrum of disease, with
a higher number of RF-secreting B cells in the seropositive patients.