Lithium chloride induces partial responsiveness to LPS in nonresponder B cells.

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.