Mouse bone marrow-derived mast cells and mast cell lines constitutively produce B cell growth and differentiation activities.

Abstract

The present report describes a novel function of mast cells that consists 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 cell 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 cells could also activate B cells, suggesting that a B cell-stimulating activity (MC-BSA) is mediated by a soluble factor(s). The addition of anti-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 mast cells with mitomycin C or actinomycin D, or paraformaldehyde fixation totally abrogated MC-BSA. Fractionation of mast cell supernatant by gel filtration chromatography resulted in four peaks, ranging from > 200 to 15 kDa, all of which were biologically active on B cells. Because mast cells are known to continuously release proteoglycans, MC-BSA was subjected to chondroitinase and heparinase treatment, but no significant 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 lymphoid organs and particularly in bone marrow.