To evaluate the mechanisms underlying the increase in serum
IgM in
primary biliary cirrhosis (PBC) studies were designed to examine
IgM production in vitro and to assess the relative contribution of intrinsic B cell activity and immunoregulatory T cell balance to
IgM synthesis. The number of peripheral blood lymphocytes (PBL) producing
IgM (spontaneous and
pokeweed mitogen (PWM) stimulated) at the end of a seven day culture period was similar in PBC patients and control subjects while the amount of
IgM synthesized (spontaneous and PWM stimulated) during this period was significantly greater in the patient group, implying that the amount of
IgM produced per B cell was increased in PBC. Co-culture of autologous and allogeneic T and B lymphocytes and irradiation of T lymphocytes from patients and normal subjects clearly implicated abnormal suppressor T cell function, rather than autonomous B cell hyperactivity, as the cause of the increased
IgM synthesis. Direct studies of T cell function indicated that although
concanavalin A (Con A) activated suppressor cells inhibited proliferation of
IgM producing B cells in the majority of PBC patients, they were unable to inhibit
IgM synthesis. The demonstration of a disparity between
IgM synthesis and the proliferation of
IgM-producing B cells, together with the observation that the abnormality of T cell function is largely confined to the control of
IgM secretion, is consistent with the presence of at least two different suppressor subpopulations regulating
IgM production. In PBC the main suppressor cell abnormality seems to affect regulation of
IgM secretion rather than B cell proliferation.