B lymphocyte function in multiple myeloma: analysis of T cell- and monocyte-dependent antibody production.
T-cell and B-cell functions were studied in 35 patients with untreated multiple myeloma (MM) and in 16 patients with MM treated with prednisolone, melphalan and vincristine. The numbers of CD4+ T cells were normal in untreated MM patients, but markedly decreased in treated patients, whereas CD8+ cell numbers were normal in untreated and treated patients. Mitogen-induced as well as antigen-induced lymphocyte proliferative responses were reduced, but not further affected by treatment. The antigen-induced proliferative responses by lymphocytes of treated, but not of untreated patients, correlated positively to the proportions of CD4+ cells among MNC. Taken together, the findings suggest selective loss of CD4+ subpopulations during cytotoxic treatment. Pokeweed mitogen (PWM)-induced Ig production was generally low, but significantly reduced Ig production was only seen in experiments employing MM B cells and monocytes co-cultured with irradiated T-enriched cells. Irradiated MM T cells displayed normal helper function when co-cultured with normal B cells stimulated with PWM. MM B cells and monocytes cultured with irradiated normal T cells produced little Ig; however, MM monocytes were not suppressive. In 2 of 3 patients with either IgG-kappa or IgA-kappa myeloma, the numbers of PWM-stimulated B cells that produced kappa chains were somewhat higher than those found among normal MNC. The impaired ability of antibody production by B cells from untreated MM patients seems to relate to intrinsic B cell defect(s) rather than to abnormal regulation by T cells or monocytes. However, disturbances in the functions of CD4+ cells may be observed in treated MM.
Petersen
J
J
Laboratory of Medical Immunology, University Hospital, Copenhagen, Denmark.
Drivsholm
A
A
Brandt
M
M
Ambjørnsen
A
A
Dickmeiss
E
E
D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000145:classification / Q000276:immunology*; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007136:Immunoglobulins