Snapper C M, Rosas F R, Kehry M R, Mond J J, Wetzler L M
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.
Infect Immun. 1997 Aug;65(8):3203-8. doi: 10.1128/iai.65.8.3203-3208.1997.
Resting B cells stimulated with dextran-conjugated anti-immunoglobulin D (anti-IgD) antibodies (anti-Ig-dex), a model for B-cell activation in response to polysaccharide antigens, proliferate but secrete little if any Ig, unless additional stimuli are present. In order to elucidate the parameters which costimulate T-cell-independent antipolysaccharide antibody responses during bacterial infections, we tested the capacities of highly purified porin proteins from Neisseria meningitidis and Neisseria gonorrhoeae to augment in vitro proliferation and induce Ig secretion by anti-Ig-dex-activated B cells. Resting B cells, from lipopolysaccharide (LPS)-nonresponsive C3H/HeJ mice, proliferated and secreted IgM in response to each of three distinct porins acting alone. Further, porins, even at concentrations that were minimally inductive when acting alone, were strongly synergistic with anti-Ig-dex for proliferation and Ig secretion. Similar synergistic effects of porins with CD40-ligand were also observed. These effects of porins were shown to occur directly at the level of the B cell. The predominant Ig isotype elicited in response to porins plus anti-Ig-dex or CD40-ligand was IgM (>97%), with the remainder comprising IgG. Surprisingly, picogram-per-milliliter amounts of neisserial LPS were also found to be highly synergistic with anti-Ig-dex for induction of IgM secretion by LPS-responsive C3H/HeN, but not C3H/HeJ, B cells. Thus, these data suggest that porins, as well as LPS, may provide critical second signals for T-cell-independent induction of polysaccharide-specific Ig in response to neisserial and other gram-negative porin-expressing bacterial pathogens, without a requirement for the participation of non-B cell types. These data may also help to explain the potent immunopotentiating effects of porins for polysaccharide-specific, as well as protein-specific, humoral responses in vivo.
用与葡聚糖偶联的抗免疫球蛋白D（抗IgD）抗体（抗Ig-葡聚糖）刺激静息B细胞，这是B细胞对多糖抗原作出反应而活化的模型，B细胞会增殖，但几乎不分泌或不分泌Ig，除非有额外的刺激。为了阐明在细菌感染期间共刺激T细胞非依赖性抗多糖抗体反应的参数，我们测试了来自脑膜炎奈瑟菌和淋病奈瑟菌的高度纯化的孔蛋白增强体外增殖以及诱导抗Ig-葡聚糖活化的B细胞分泌Ig的能力。来自对脂多糖（LPS）无反应的C3H/HeJ小鼠的静息B细胞，对单独作用的三种不同孔蛋白中的每一种都有增殖并分泌IgM的反应。此外，孔蛋白即使在单独作用时诱导作用最小的浓度下，与抗Ig-葡聚糖在增殖和Ig分泌方面也有很强的协同作用。还观察到孔蛋白与CD40配体有类似的协同作用。已证明孔蛋白的这些作用直接发生在B细胞水平。对孔蛋白加抗Ig-葡聚糖或CD40配体作出反应而产生的主要Ig同种型是IgM（>97%），其余为IgG。令人惊讶的是，还发现皮克/毫升量的奈瑟菌LPS与抗Ig-葡聚糖在诱导LPS反应性C3H/HeN（而非C3H/HeJ）B细胞分泌IgM方面有高度协同作用。因此，这些数据表明，孔蛋白以及LPS可能为T细胞非依赖性诱导针对奈瑟菌和其他表达孔蛋白的革兰氏阴性细菌病原体的多糖特异性Ig提供关键的第二信号，而无需非B细胞类型的参与。这些数据也可能有助于解释孔蛋白对体内多糖特异性以及蛋白质特异性体液反应的强大免疫增强作用。
