INHIBITION OF CLASS SWITCH RECOMBINATION IN PLASMA-CELLS

We investigated whether the absence of class switch recombination in plasma cells is due to the lack of factors required for class switching or to an inhibitor of the recombination present in these cells. Polyclonally activated B cells, actively performing class switch recombination, were fused with IgM-producing PC140 hybridoma cells, i.e., transformed plasma cells, which are capable of undergoing spontaneous class switching, although at low frequency (10(-5)). The switch regions S mu and S gamma 1 are in germline configuration and the genes are demethylated as required for accessibility. In the hybrid-hybridomas the frequency of class switch recombination is not enhanced for PC140 IgH loci but rather inhibited for the IgH loci of the LPS blasts. Thus, fusion of class-switch-performing B cells with the higher differentiated plasma cells, which no longer switch, results in a shutdown of class switching. This points to an inhibitor of the class switch recombination present in plasma cells. (C) 1994 Academic Press, Inc.