INTERLEUKIN-2-DEPENDENT AUGMENTATION OF THE ANTI-TNP ANTIBODY-PRODUCTION BY SODIUM-BUTYRATE IN CULTURED MURINE SPLENIC B-CELLS

Previously we found that sodium butyrate (NaBu) markedly enhanced prod uction of the antibody specific for a T-cell-dependent antigen, sheep red blood cells (SRBC) in murine splenocytes (Kishiro, Y., Ueda, K., F ujiwara, M. and Yamamoto, I., Jpn J. Phamacol., 1994 66, 369-376. To g ain a better understanding of the target cells for NaBu's action on an tibody responses, we have utilized the T-cell-independent antigen, tri nitrophenyl-lypopolysaccharide (TNP-LPS) as a stimulant and have exami ned an effect of NaBu on the anti-TNP antibody production in vitro. Na Bu markedly increased the anti-TNP plaque-forming cell (PFC) responses in murine whole splenocytes, but not in murine splenic B cells. Addit ion of T-cells or the concanavalin A supernatant (GAS) from murine spl enocytes to the B cell cultures completely restored the enhancing effe ct of NaBu. This effect of CAS was totally blocked by an anti-interleu kin (IL)-2 antibody and partially by an anti-IL-1 beta or anti-IL-4 an tibody. The full enhancing effect of NaBu was also detected when IL-2 was added to the B cell cultures, while IL-2 alone had no stimulatory effect on the control PFC response. IL-1 beta alone significantly stim ulated the antibody production and adding NaBu to this IL-1 beta-suppl emented culture caused a further increase. Neither IL-4 alone nor NaBu plus IL-4 had any effect on the PFC response. NaBu did not affect the expression of the IL-2 receptor alpha-and beta-chains in B cells stim ulated with TNP-LPS. These results suggest that NaBu is an agent that promotes B cell differentiation in vitro in an IL-2-dependent manner. (C) 1997 International Society for Immunopharmacology.