An increase in histone acetylation and IL-2 antagonizing the immunoinhibitory effect are necessary for augmentation by butyrate of in vitro anti-TNP antibody production

We investigated the role of histone acetylation in the promotion of antigen -specific antibody production in murine B cells induced bg sodium butyrate (NaBu) plus interleukin 2 (IL-2). NaBu dose dependently increased the acety lation levels of histone H4 at concentrations which effectively enhanced an ti-trinitrophenyl (TNP) antibody production in the presence of IL-2. Among other short-chain fatty acids and NaBu analogs, propionate, valerate and vi nylacetate were effective in the presence of IL-2 in increasing both antibo dy production and the histone H4 acetylation level, but acetate, alpha-, be ta- and gamma-hydroxybutyrates and alpha-, beta- and gamma-aminobutyrates w ere not effective, even in the presence of IL-2. The effect of the specific histone deacetylase inhibitor trichostatin A (TSA), which enhances anti-TN P antibody production without IL-2, was markedly inhibited by adding NaBu s imultaneously. However, the effect of TSA was neither inhibited nor potenti ated by NaBu in the presence of IL-2. Splenic B cells treated with NaBu, TS A and both together in the presence or absence of IL-2 showed almost the sa me increased acetylation level of histone H4. These results suggest that th e NaBu-induced enhancement of anti-TNP antibody production in the presence of IL-2 is mediated through a moderate increase in the level of histone ace tylation and that NaBu has both stimulating and inhibiting activities for a nti-TNP antibody production, the latter of which is overcome by IL-2.