In vitro studies on the mechanism of increased serum IgM levels in primary biliary cirrhosis.
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.
Nouri-Aria
K T
KT
Hegarty
J E
JE
Neuberger
J
J
Eddleston
A L
AL
Williams
R
R
D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008938:Mitosis; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D003208:Concanavalin A