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-linking of membrane immunoglobulin (mIg) 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 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-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-Fc gamma RII mAb to prevent cross-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 cell death; (b) increased cross-linking of mIgD 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 mIgD may be necessary to cause B cell death; (e) mIgMdull but not mIgMbright B cells are lost in mice injected with anti-IgD mAbs; and (f) T cell help prevents or minimizes B cell death.
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
F D
FD
Finkelman
J M
JM
Holmes
O I
OI
Dukhanina
S C
SC
Morris
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D016923:Cell Death / Q000276:immunology; D005260:Female; D007072:Immunoglobulin D / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D015851:Interleukin-7 / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D015851:Interleukin-7