By employing the specific
histone deacetylase inhibitor trichostatin A (
TSA), we investigated whether
histone acetylation modulates the production of
antigen-specific
antibodies in murine splenocytes in vitro.
TSA caused a marked increase in both anti-sheep red blood cell (SRBC) and anti-trinitrophenyl (TNP) plaque-forming cell (PFC) responses in splenocytes at much lower concentrations than
sodium butyrate. It also dose dependently augmented the production of anti-trinitrophenyl
antibodies in splenic B cells with a concomitant, moderate increase in the level of
histone H4 acetylation. Its optimal concentration for promoting the production of these
antibodies was 10 nM. However, to gain such an effect on antibody production,
TSA had to be added to cells before Day 2 in culture.
Trichostatin C, an analog of
TSA and a less potent inducer of Friend
leukemia cell differentiation, also increased both the anti-trinitrophenyl PFC response and
histone H4 acetylation in B cells, but at higher concentrations than
TSA.
TSA did not stimulate the production of
lipopolysaccharide-induced polyclonal
immunoglobulin M in B cells. These results suggest that a moderate increase in
histone acetylation may play a significant role in promoting
antigen-specific antibody production in B cells.