DIFFERENT NUCLEAR SIGNALS ARE ACTIVATED BY THE B-CELL RECEPTOR DURINGPOSITIVE VERSUS NEGATIVE SIGNALING

It is not known how immunogenic versus tolerogenic cellular responses are signaled by receptors such as the B cell antigen receptor (BCR). H ere we compare BCR signaling in naive cells that respond positively to foreign antigen and self-tolerant cells that respond negatively to se lf-antigen. In naive cells, foreign antigen triggered a Targe biphasic calcium response and activated nuclear signals through NF-AT, NF-kapp a B, JNK, and ERK/pp90rsk. In tolerant B cells, self-antigen stimulate d low calcium oscillations and activated NF-AT and ERK/pp90rsk but not NF-kappa B or JNK. Self-reactive B cells lacking the phosphatase CD45 did not exhibit calcium oscillations or ERK/pp90rsk activation, nor d id they repond negatively to self-antigen. These data reveal striking biochemical differences in BCR signaling to the nucleus during positiv e selection by foreign antigens and negative selection by self-antigen s.