Kehrl J H, Fauci A S
Bull Eur Physiopathol Respir. 1983 Mar-Apr;19(2):227-34.
The in vivo and in vitro immune responses following in vivo immunization with pneumococcal polysaccharides (PPS) has been analyzed in man. Within 6 days following immunization, specific PPS antigen-binding cells (ABC), specific plaque-forming cells (PFC) and cells capable of spontaneously synthesizing in vitro substantial amounts of specific anti-PPS IgG and IgA and lesser amounts of specific IgM appeared in the peripheral blood. The ABC, PFC and total amounts of specific spontaneous antibody production in vitro followed nearly identical kinetics after immunization. The ABC were isolated and shown to be large B cells, predominantly surface IgG positive and surface IgD negative, and to express an activation antigen called 4F2. Low doses of in vitro irradiation markedly inhibited spontaneous anti-PPS antibody production by lymphocytes obtained 7 or 8 days after immunization, suggesting a requirement for in vitro proliferation for full expression in vitro of antibody secretion following in vivo activation. Spontaneous secretion by B lymphocytes in vitro was independent of T cells, unmodified by the addition of T cell factors, and readily suppressible by pokeweed mitogen (PWM). These findings strongly suggest that the in vivo immunization with PPS delivered to these spontaneously secreting PPS-specific B cells the signals for proliferation as well as differentiation, both of which were expressed in vitro. By 2 weeks after immunization, spontaneous anti-PPS antibody production in vitro was no longer detected. Subsequent stimulation of lymphocytes with a wide range of concentrations of specific antigen did not trigger either proliferation or specific antibody synthesis. Despite the unresponsiveness of these cells to antigenic stimulation, they were capable of specific anti-PPS antibody production following stimulation with PWM. This finding demonstrates that PPS-specific B cells are indeed present in the circulation at this time. The lack of ability of PPS antigen itself to trigger these B cells at this point in time strongly suggests that PPS-specific T cells are either not present or are untriggerable, and PWM can bypass the need for specific T cells by polyclonally stimulating the T cell pool. This system should prove useful in delineating certain aspects of B cell physiology not readily approachable with standard soluble protein antigens.
已对人体接种肺炎球菌多糖（PPS）后的体内和体外免疫反应进行了分析。免疫后6天内，外周血中出现了特异性PPS抗原结合细胞（ABC）、特异性空斑形成细胞（PFC）以及能够在体外自发合成大量特异性抗PPS IgG和IgA以及少量特异性IgM的细胞。免疫后，ABC、PFC以及体外特异性自发抗体产生的总量遵循几乎相同的动力学。ABC被分离出来，显示为大B细胞，主要表面IgG阳性且表面IgD阴性，并表达一种名为4F2的活化抗原。低剂量的体外照射显著抑制了免疫后7或8天获得的淋巴细胞的自发抗PPS抗体产生，这表明体内激活后抗体分泌在体外充分表达需要体外增殖。B淋巴细胞在体外的自发分泌独立于T细胞，不受添加T细胞因子的影响，且易被商陆丝裂原（PWM）抑制。这些发现强烈表明，用PPS进行体内免疫为这些自发分泌PPS特异性的B细胞提供了增殖和分化的信号，两者均在体外表达。免疫后2周，体外不再检测到自发抗PPS抗体产生。随后用各种浓度的特异性抗原刺激淋巴细胞，既未引发增殖也未引发特异性抗体合成。尽管这些细胞对抗抗原刺激无反应，但在用PWM刺激后它们能够产生特异性抗PPS抗体。这一发现表明此时循环中确实存在PPS特异性B细胞。此时PPS抗原本身无法触发这些B细胞，这强烈表明要么不存在PPS特异性T细胞，要么它们无法被触发，而PWM可以通过多克隆刺激T细胞池来绕过对特异性T细胞的需求。该系统应有助于阐明B细胞生理学中某些用标准可溶性蛋白质抗原不易研究的方面。
