Kodo H, Gale R P, Saxon A
J Clin Invest. 1984 May;73(5):1377-84. doi: 10.1172/JCI111341.
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.
正常志愿者接受破伤风类毒素的初次或加强免疫。在免疫后长达28天获取骨髓和外周血单核细胞，并分析其总Ig和破伤风类毒素特异性抗体的合成情况。细胞在有或无商陆有丝分裂原（PWM）的情况下体外培养3天或7天。通过放射免疫测定法测定破伤风IgG和IgM抗体（IgG-Tet和IgM-Tet）以及总IgG和IgM的合成。在破伤风加强免疫后，在骨髓中检测到四个功能性B细胞亚群：（a）自发合成IgG-Tet的B细胞在免疫后第7天出现，但在第21天无法检测到；（b）用PWM刺激后合成IgG-Tet的B细胞在第21天后出现并持续超过1个月；（c）在PWM存在下合成IgM-Tet的B细胞在免疫前后均可检测到；（d）自发合成IgM-Tet的B细胞在第7天出现并在第21天无法检测到。与所描述的其他三种类型的骨髓B细胞相比，在外周血中未检测到这种不依赖PWM的合成IgM-Tet的B细胞的第四亚群。初次免疫后，尽管三名受试者中有两名的IgM-Tet略有升高，但在血液或骨髓中未检测到自发产生抗体的细胞。在骨髓中，仅可见IgM-Tet PWM诱导性细胞，尽管在循环中检测到有丝分裂原反应性IgM和IgG-Tet细胞。IgM-Tet PWM反应性细胞甚至在初次抗原暴露之前就已存在，似乎代表参与抗体反应的初始B细胞。这些数据表明，免疫后存在特定时间，此时不同功能类别的抗破伤风合成B细胞和记忆B细胞出现在人类骨髓中。了解这些数据对于制定在骨髓移植环境中将免疫记忆从供体转移到受体的策略可能很重要。
