title: Antibody synthesis by bone marrow cells in vitro following primary and booster tetanus toxoid immunization in humans.
abstract: Normal volunteers received either initial or booster immunization with tetanus toxoid. Bone marrow and peripheral blood mononuclear cells were obtained for up to 28 d after immunization and were analyzed for synthesis of total Ig and specific antibodies to tetanus toxoid. Cells were cultured in vitro for 3 or 7 d with or without pokeweed mitogen (PWM). Synthesis of IgG and IgM antibodies to tetanus (IgG-Tet and IgM-Tet) and total IgG and IgM was determined by radioimmunoassay. Four functional B cell subpopulations were detected in the bone marrow after booster tetanus immunization: (a) B cells that spontaneously synthesized IgG-Tet appeared on day 7 after immunization but were undetectable by day 21; (b) B cells that synthesized IgG-Tet after stimulation with PWM appeared after day 21 and persisted for greater than 1 mo; (c) B cells that synthesized IgM-Tet in the presence of PWM were detectable before and after immunization; and (d) B cells that spontaneously synthesized IgM-Tet appeared on day 7 and were undetectable by day 21. In contrast to the other three types of bone marrow B cells described, this fourth subpopulation of PWM-independent IgM-Tet-synthesizing B cells was not detected in the peripheral blood. After primary immunization, no spontaneous antibody-producing cells were detected in the blood or bone marrow, although there was a small rise in IgM-Tet in two of three subjects. In the bone marrow, only IgM-Tet PWM-inducible cells were seen, although mitogen-responsive IgM and IgG-Tet cells were detected in the circulation. The IgM-Tet PWM-reactive cells were present even before primary antigen exposure and appear to represent the initial B cells involved in the antibody response. These data indicate that there are specific times after immunization when different functional classes of anti-Tet-synthesizing B cells and memory B cells appear in human bone marrow. Knowledge of these data may be important in developing a strategy for the transfer of immune memory from donors to recipients in the setting of bone marrow transplantation.
mesh_terms: D000328:Adult; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007114:Immunization; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D011043:Pokeweed Mitogens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D013742:Tetanus / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011043:Pokeweed Mitogens; D013745:Tetanus Toxoid