MOUSE BONE-MARROW-DERIVED MAST-CELLS AND MAST-CELL LINES CONSTITUTIVELY PRODUCE B-CELL GROWTH AND DIFFERENTIATION ACTIVITIES

The present report describes a novel function of mast cells that consi sts of a B cell growth activity. The B cell response occurred without any stimulation or preactivation of mast cells, A small number of mast cells was required, since mast cell/B cell ratios as low as 1/100 to 1/10,000 lead to effective B cell activation. Mast cell-dependent B ce ll activation resulted, within 48 h of incubation, in blast formation, proliferation, and IgM production. Both low and high density B cells were responsive to mast cells. Supernatants from unstimulated mast cel ls could also activate B cells, suggesting that a B cell-stimulating a ctivity (MC-BSA) is mediated by a soluble factor(s), The addition of a nti-IL-4 or anti-IL-6 mAbs or even proteases to the mast cell-derived supernatants did not alter B cell activation. However, treatment of ma st cells with mitomycin C or actinomycin D, or paraformaldehyde fixati on totally abrogated MC-BSA, Fractionation of mast cell supernatant by gel filtration chromatography resulted in four peaks, ranging from >2 00 to 15 kDa, all of which were biologically active on B cells. Becaus e mast cells are known to continuously release proteoglycans, MC-BSA w as subjected to chondroitinase and heparinase treatment, but no signif icant inhibition of B cell activation was obtained, This direct T cell -independent stimulatory effect of mast cells on B cells could account for a mechanism by which plasma cells are continuously produced in ly mphoid organs and particularly in hone marrow.