Induction of light chain replacement in human plasma cells by caffeine is independent from both the upregulation of RAG protein expression and germ line transcription

When some human plasma cell lines are cultured with concanavalin A, the ori ginal light chain is replaced with another light chain which results from s econdary VJ recombination (light chain shifting), We examined various intra cellular factors involved in the induction of light chain shifting. Light c hain shifting can be induced upon treatment with agents with phosphatase in hibitory activity such as caffeine and okadaic acid. Although the plasma ce lls used express both RAG-1 and RAG-2, the expression level of these protei ns was not affected by caffeine or okadaic acid. Transcription of the germ line locus, which correlates to the locus activation for rearrangement, is also not influenced by phosphatase inhibition. However, the amount of signa l broken-ended DMA intermediates generated during V(D)J rearrangement was s hown to increase upon caffeine or okadaic acid treatment, The inhibitory ac tivity of caffeine on phosphatase was the same as okadaic acid. However, ca ffeine exhibited much higher activity for VJ coding joint formation than ok adaic acid. Therefore, although phosphatase inhibition might act, in part, on a mechanism by which V(D)J recombinase activity is regulated within the human plasma cells, other factor(s) are probably also involved in the proce ss.