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The ability to identify and remove potentially dangerous foreign organisms and proteins is critical to the survival of a species. In humans, IgG antibodies serve to recognize such foreign antigens and to facilitate their removal. The latter process involves several hematopoietic cells, including those of the macrophage phagocytic system, which express Fcγ receptors. These receptors specifically recognize the Fc domain of IgG antibody. On the surface of hematopoietic cells these Fcγ receptors mediate cell attachment and stimulate several signal transduction events, including those which lead to phagocytosis. Moreover, their perturbation can lead to the generation and release of mediators and enzymes involved in inflammation and in the pathogenesis of autoimmune diseases.

The thymus, with its striking B cell infiltrates, is widely regarded as an important element in the pathogenesis of myasthenia gravis (MG) but its role remains to be elucidated. To gain further insight into the functional properties of MG thymic B cells, we studied the heavy chain isotype of immunoglobulin they produced in vitro in response to the T cell-dependent polyclonal activator pokeweed mitogen (PWM). MG thymic cells secreted prominent amounts of IgG but little IgM. In contrast, peripheral blood mononuclear cells (PBM) of the same subjects secreted similar amounts of IgG and IgM as did PBM of control subjects. In cell admixture experiments, MG thymic T cells, like PBM T cells, helped autologous PBM B cells produce IgM as well as IgG, although the overall magnitude of help for both isotypes appeared less than that of PBM T cells. Thus, in response to PWM, MG thymic B cells are largely committed to an IgG response and this likely reflects the intrinsic properties of these cells rather than the immunoregulatory properties of thymic T cells. This IgG isotype switch likely reflects in vivo activation events.

The level of circulating cells secreting IgG, IgM, and IgA (IgSC) provides insight into the degree of in vivo polyclonal B-cell activation (PBA). Patients with rheumatoid arthritis (RA) exhibit abnormalities in humoral immune responses suggestive of augmented in vivo polyclonal B-cell activation. Therefore, a protein A reverse hemolytic plaque assay was used to measure the level of circulating IgSC in 32 RA patients. The mean level of circulating IgSC in RA patients was 3602 +/- 747 (SEM) compared to a mean of 1407 +/- 443 in patients with other types of arthritis and 1253 +/- 216 (P less than 0.02) in healthy volunteers. Levels found in RA patients did not appear to reflect disease activity or concomitant corticosteroid therapy. However, a subset of RA patients receiving gold therapy had levels of IgSC (1381 +/- 501) similar to those seen in healthy volunteers (P greater than 0.5). These data are consistent with augmented in vivo polyclonal B-cell activation in RA. In addition they suggest that gold affects mechanisms controlling in vivo B-cell activation.