Issues

Diagram of the RP-105–mediated signal transduction in B cells. RP-105 is a mature B cell–specific transmembrane protein with a high degree of homology to toll protein (Miyake, K., Y. Yamashita, M. Ogata, T. Sudo, and M. Kimoto. 1995. J. Immunol. 154:3333–3340). A possible involvement of toll in innate immune responses in vivo (Medzhitov, R., and C.A. Janeway, Jr. 1997. Cell. 91:295–298) suggests a similar function for RP-105 in B cells. The antibody-mediated cross-linking of RP-105 in vitro induces B cell activation that could be inhibited by simultaneous cross-linking of B cell receptor (BCR). The results of genetic and biochemical analysis of RP-105–mediated B cell signaling show that signaling through both BCR and RP-105 occurs via the Lyn-Btk-PKCβI/II signaling chain, followed by activation of mitogen-activated protein kinases. These data demonstrate the molecular mechanism of B cell activation by RP-105 and its counterregulation by BCR. See related article in this issue by Chan et al., pp. 93–101.