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.
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D051379:Mice; D008809:Mice, Inbred C3H; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D013154:Spleen / Q000276:immunology
D002712:Chlorides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; D012313:RNA; D004247:DNA; D008094:Lithium; D018021:Lithium Chloride