Cross - linking of Membrane Immunoglobulln D , in the Absence of T Cell Help , Kills Mature B Cells In Vivo

In vivo experiments were performed to determine whether the cross-linking of membrane immunoglobulin (mlg) D on mature B cells, in the absence of T cell help, leads to B cell death. Mice were injected with either a monoclonal antibody (mAb) that cross-links mlgD effectively or a mAb that binds to mlgD avidly but cross-links it to a limited extent, and effects on B cell number and B cell Ia, mlgM, and mlgD expression were observed. In most experiments, mice were pretreated with anti-interleukin 7 mAb to prevent the generation of new bone marrow B cells, and with anti-CD4 mAb to prevent the generation of T cell help. In some experiments, mice also received anti-Fc3,RII mAb to prevent cross-linking of mlgD with Fc'yRII, and cobra venom factor to prevent possible mlg-complement receptor interactions and complement-mediated killing of B cells. The results of these studies demonstrate that (a) even limited cross-linking of mlgD on mature B cells can lead to B cell death; (b) increased cross-linking of mlgD leads to increased B cell 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 modulation of mlgD may be necessary to cause B cell death; (e) mlgM a~ but not mlgM bri~h' B cells are lost in mice injected with antiIgD mAbs; and (f) T cell help prevents or minimizes B cell death.