B-LYMPHOCYTE SENSITIVITY TO IGM RECEPTOR LIGATION IS INDEPENDENT OF MATURATION STAGE AND LOCALLY DETERMINED BY MACROPHAGE-DERIVED IFN-BETA

Compartmentation of B lymphocyte populations is associated with differ ences in both development stage and sensitivity to Ig (sIg)-dependent triggering. In order to characterize the factors that contribute in se tting the level of sensitivity of a B cell, we quantified sIgM-depende nt regulation of Ig secretion in purified mature and immature B cells after ex vivo and in vivo modification of their environment. These ana lyses formally demonstrate that the bone marrow (BM) microenvironment locally induces high B cell sensitivity to sIgM ligation irrespective of differentiation stage. We further provide evidence that BM macropha ges create a dominant environment that enhances B cell sensitivity to B cell receptor triggering. Finally, using ex vivo assays as well as t ype I IFN receptor-deficient mice we show that IFN-beta produced by re sident BM macrophages is necessary and sufficient to define B cell sen sitivity. Implications of these findings for the understanding of B ce ll selection processes are discussed.