Pokeweed mitogen-induced immunoglobulin secretory responses of thymic B cells in myasthenia gravis: Selective secretion of IgG versus IgM cannot be explained by helper functions of thymic T cells

Abstract

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.