Effect of a synthetic adjuvant on the induction of primary immune responses in T cell-depleted spleen cultures.
N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide) stimulates in vitro primary immune responses to SRBC in T cell-depleted (nude) spleen cultures. The stimulation of immune responses by muramyl peptide was antigen dependent. A microculture system was used to compare the T cell-replacing activities of several structural analogues of muramyl dipeptide and to compare the activity of muramyl dipeptide to helper T cells. In a limiting dilution analysis with excess helper T cells or muramyl dipeptide, the frequency of B cell precursors that respond to SRBC was similar, ranging from 1.5 to 5 X 10(-5). Decreasing the cell density in microcultures did not affect the efficiency of B cell precursor responses in the presence of muramyl dipeptide. Muramyl dipeptide was examined for mitogenic activity in spleen cell cultures. In serum-free medium, muramyl dipeptide stimulates slight (3-fold) increases in DNA synthetic activity. In medium supplemented with 5 to 20% fetal calf serum, muramyl dipeptide showed no significant mitogenic activity. There are a number of possible explanations for the T cell-replacing activity of muramyl dipeptide. The most likely is that muramyl dipeptide interacts directly with B cells to mimic the helper T cell signal in the inductive stimulus.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D008211:Lymphocyte Cooperation; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008934:Mitogens; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D008934:Mitogens