Ishizaka S, Möller G
Nature. 1982 Sep 23;299(5881):363-5. doi: 10.1038/299363a0.
The lipopolysaccharide (LPS)-nonresponder mouse strains C3H/HeJ, C57BL/10ScCR and C57BL/10ScN do not respond to LPS acting as a polyclonal B-cell activator, a mitogen, or an adjuvant. The genetic basis for the defective LPS response has been extensive studied in C3H/HeJ and C57BL/10ScCR mice, in which it was demonstrated that a single gene locus on chromosome 4 was responsible for LPS unresponsiveness. Lithium chloride, a potent inhibitor of adenylate cyclase, not only improved lymphocyte activity in a patient with adenosine deaminase deficiency but also enhanced the phytohaemagglutinin (PHA)-induced responses of normal human lymphocytes. Therefore, we investigated whether LiCl could restore LPS responsiveness in spleen cells of C3H/HeJ mice. We show here that LPS, in the presence of LiCl, induced polyclonal IgM and IgG antibody formation and DNA synthesis in C3H/HeJ mouse spleen cells in vitro. Moreover, LiCl (10 mM), which by itself is non-mitogenic, increased RNA synthesis in spleen cells from both LPS-nonresponder and high responders strains; in contrast, LPS failed to increase RNA synthesis in cells from such LPS-nonresponder strains as C3H/HeJ and B10ScCr mice.
脂多糖（LPS）无反应小鼠品系C3H/HeJ、C57BL/10ScCR和C57BL/10ScN对LPS作为多克隆B细胞激活剂、促有丝分裂原或佐剂的作用无反应。在C3H/HeJ和C57BL/10ScCR小鼠中对LPS反应缺陷的遗传基础进行了广泛研究，结果表明4号染色体上的一个单基因座导致了LPS无反应性。氯化锂是腺苷酸环化酶的有效抑制剂，它不仅改善了腺苷脱氨酶缺乏患者的淋巴细胞活性，还增强了正常人淋巴细胞对植物血凝素（PHA）诱导的反应。因此，我们研究了LiCl是否能恢复C3H/HeJ小鼠脾细胞对LPS的反应性。我们在此表明，在LiCl存在的情况下，LPS在体外诱导C3H/HeJ小鼠脾细胞产生多克隆IgM和IgG抗体并促进DNA合成。此外，本身无促有丝分裂作用的LiCl（10 mM）增加了LPS无反应品系和高反应品系脾细胞中的RNA合成；相反，LPS未能增加C3H/HeJ和B10ScCr小鼠等LPS无反应品系细胞中的RNA合成。
