To study antibody (Ab) biosynthesis in
rheumatoid arthritis (RA), the
immunoglobulin (Ig)M anti-Fc, anti-Fab', and
antistreptokinase-
streptodornase (SKSD) produced by peripheral blood lymphocytes (PBL) were measured at intervals from 1 to 19 d in culture. PBL from 17 seropositive patients with active RA and 30 age-matched controls were evaluated. Within the first 24 h, PBL from six of eight patients released >30 ng
IgM anti-Fc, even in the absence of
pokeweed mitogen (PWM). This early release of Ab was blocked by
cycloheximide. With or without PWM, PBL from normal donors did not release
IgM anti-Fc until after 3-5 d in vitro. By day 9, unstimulated PBL from seven patients made > 100 ng
IgM anti-Fc. Un-stimulated PBL from normals never made >95 ng of this Ab. When PWM was added, PBL from normal donors released as much
IgM anti-Fc as was found in RA donor cultures. Paradoxically, addition of PWM to PBL of RA patients suppressed release of
IgM anti-Fc in 4 of 17 cases to levels significantly below those found in unstimulated cultures of the same cells. Without PWM, PBL from RA donors frequently failed to make
IgM anti-SKSD (P < 0.05 compared with normal donors' cells). With PWM, the quantities of
IgM anti-SKSD released were comparable. Fluctuations in
IgM anti-Fab' levels during the life-time of these cultures were sufficient to suggest that these Ab may be taken up in
immune complexes. This hypothesis was verified by acidifying (pH 3.1) culture supernatants to which (125)I-Fab' had been added previously. The samples were then neutralized (pH 7.6) and 12%
polyethylene glycol was added to separate free from antibody-bound (125)I-Fab'. This procedure increased the quantity of (125)I-Fab' precipitated by > 10-fold in some cases. These studies suggest that there are a variety of abnormalities in Ab biosynthesis in RA. These include spontaneous synthesis of comparatively large quantities of
IgM anti-Fc, relatively suppressed release of
IgM anti-SKSD, and a paradoxical reduction, in some cases, in the biosynthesis of
IgM anti-Fc after addition of PWM.