Dusheiko G M, Hoofnagle J H, Cooksley W G, James S P, Jones E A
J Clin Invest. 1983 May;71(5):1104-13. doi: 10.1172/jci110860.
It has been postulated that host immune defects are responsible for the development and persistence of the hepatitis B surface antigen (HBsAg) carrier state. The nature of these defects is unknown, but the absence of a readily detectable antibody response to HBsAg (anti-HBs) may be important. The synthesis of both anti-HBs and antibody to hepatitis B core antigen (anti-HBc) in cultures containing peripheral blood mononuclear cells from chronic HBsAg carriers and from control (antibody-positive) patients was measured in the presence of pokeweed mitogen. Similar amounts of polyclonal IgG and IgM were synthesized by cultures containing lymphocytes from chronic carriers and controls. Anti-HBc was detectable in lymphocyte supernatants from 2 of 20 controls and from 21 of 29 carriers. The presence of anti-HBc synthesis in vitro correlated with high serum titers of anti-HBc. In contrast, anti-HBs was detected in lymphocyte supernatants from 6 of 20 controls (predominantly in those who had high serum titers of anti-HBs) but in none of the supernatants from 29 HBsAg carriers. In order to identify the mechanisms for the lack of detectable anti-HBs synthesis by chronic HBsAg carrier lymphocytes, co-culture experiments were performed using T and B lymphocyte fractions that had been purified by affinity chromatography. B lymphocytes from carriers co-cultured with allogeneic irradiated ("helper") T lymphocytes from controls synthesized normal amounts of IgG, IgM, and anti-HBc but still did not synthesize detectable amounts of anti-HBs. In the converse experiments, B lymphocytes from controls were co-cultured with irradiated T lymphocytes from carriers. The T lymphocytes from 16 of 24 carriers augmented anti-HBs production by control B cells normally, the remaining eight did not. Finally, mixtures of control B cells and control irradiated T lymphocytes were co-cultured with T lymphocytes from chronic HBsAg carriers. 5 of 12 carriers demonstrated active suppression of anti-HBs production, and in three this suppression was specific, as IgG and IgM production remained normal. We conclude that chronic HBsAg carriers have a specific B lymphocyte defect in anti-HBs production. In addition, defects in the function of regulatory T lymphocytes may contribute to the absence of anti-HBs synthesis in some HBsAg carriers.
据推测，宿主免疫缺陷是乙肝表面抗原（HBsAg）携带者状态发生及持续存在的原因。这些缺陷的本质尚不清楚，但对HBsAg缺乏易于检测到的抗体反应（抗-HBs）可能很重要。在有商陆丝裂原存在的情况下，检测了含有慢性HBsAg携带者和对照（抗体阳性）患者外周血单个核细胞的培养物中抗-HBs和乙肝核心抗原抗体（抗-HBc）的合成情况。含有慢性携带者和对照者淋巴细胞的培养物合成的多克隆IgG和IgM量相似。在20名对照者中的2名以及29名携带者中的21名的淋巴细胞上清液中可检测到抗-HBc。体外抗-HBc合成的存在与抗-HBc的高血清滴度相关。相比之下，在20名对照者中的6名（主要是那些抗-HBs血清滴度高的人）的淋巴细胞上清液中检测到了抗-HBs，但在29名HBsAg携带者的上清液中均未检测到。为了确定慢性HBsAg携带者淋巴细胞缺乏可检测到的抗-HBs合成的机制，使用通过亲和层析纯化的T和B淋巴细胞组分进行了共培养实验。与来自对照的同种异体照射（“辅助”）T淋巴细胞共培养的携带者B淋巴细胞合成了正常量的IgG、IgM和抗-HBc，但仍未合成可检测量的抗-HBs。在相反的实验中，将对照的B淋巴细胞与来自携带者的照射T淋巴细胞共培养。24名携带者中的16名的T淋巴细胞正常增强了对照B细胞的抗-HBs产生，其余8名则没有。最后，将对照B细胞和对照照射T淋巴细胞的混合物与慢性HBsAg携带者的T淋巴细胞共培养。12名携带者中的5名表现出对抗-HBs产生的主动抑制，其中3名的这种抑制是特异性的，因为IgG和IgM产生仍正常。我们得出结论，慢性HBsAg携带者在抗-HBs产生方面存在特异性B淋巴细胞缺陷。此外，调节性T淋巴细胞功能缺陷可能导致一些HBsAg携带者缺乏抗-HBs合成。
