MODULATION OF EXPRESSION OF CLASS-II MHC AND CD40 MOLECULES IN MURINEB-CELLS BY VARIOUS MURAMYL DIPEPTIDES

Several compounds of the MDP (muramyl dipeptide) series which have the capacity to enhance the immune response to antigens exerted a comitog enic effect on murine splenic B cells. The expression of surface class II major histocompatibility and CD40 antigens was used to more accura tely evaluate the comparative influence of the synthetic agents on mat ure B cells and on the pre-B cell line 70Z/3. MDP and two adjuvant-act ive analogs enhanced expression of both surface molecules and increase d the response to lipopolysaccharide (LPS) or interferon-gamma (IFN-ga mma) in splenic B cells. The three synthetic adjuvants alone did not l ead to expression of cell-surface I-A(d) or CD40 in 70Z/3 cells, indic ating that they were unable by themselves to achieve differentiation o f pre-B cells to a mature B cell phenotype. However, they increased th e CD40 level induced by treatment with LPS. In this cell line, the res ponse (CD40 protein and mRNA) to IFN-gamma was strongly increased by M DP but not by the two other compounds. Actually, MDP was the only adju vant among the three compounds to functionally activate the transcript ion factor NF-kappa B, to induce kappa transcription, and to stimulate surface kappa light-chain expression in 70Z/3 cells. The response to muramyl dipeptides in mature splenic B cells could appear independent of the transcription factor. (C) 1996 Academic Press, Inc.