CROSS-LINKING OF MEMBRANE IMMUNOGLOBULIN-D, IN THE ABSENCE OF T-CELL HELP, KILLS MATURE B-CELLS IN-VIVO

In vivo experiments were performed to determine whether the cross-link ing of membrane immunoglobulin (mIg) D on mature B cells, in the absen ce of T cell help, leads to B cell death. Mice were injected with eith er a monoclonal antibody (mAb) that cross-links mIgD effectively or a mAb that binds to mIgD avidly but cross-links it to a limited extent, and effects on B cell number and B cell Ia, mIgM, and mIgD expression were observed. In most experiments, mice were pretreated with anti-int erleukin 7 mAb to prevent the generation of new bone marrow B cells, a nd with anti-CD4 mAb to prevent the generation of T cell help. In some experiments, mice also received anti-Fc gamma RII mAb to prevent cros s-linking of mIgD with Fc gamma RII, and cobra venom factor to prevent possible mig-complement receptor interactions and complement-mediated killing of B cells. The results of these studies demonstrate that (a) even limited cross-linking of mIgD on mature B cells can lead to B ce ll death; (b) increased cross-linking of mIgD leads to increased B cel l death; (c) the loss of B cells is first detected 2 d after anti-IgD mAb injection and increases during the subsequent 3 d; (d) sustained m odulation of mIgD may be necessary to cause B cell death; (e) mIgM(dul l) but not mIgM(bright) B cells are lost in mice injected with anti-Ig D mAbs; and (f) T cell help prevents or minimizes B cell death.