Ligation of major histocompatibility complex class II molecules mediates apoptotic cell death in resting B lymphocytes.
Class II major histocompatibility complex-encoded molecules expressed on the surface of primed B lymphocytes function as restriction elements for presentation of antigen to T lymphocytes, an interaction that ultimately leads to activation and differentiation of both cell types. The engagement of class II on a resting B cell, on the other hand, inhibits subsequent B-cell growth and activation. Our studies show that treatment of resting B lymphocytes with anti-class II antibodies, or with other agents (dibutyryl cAMP or isoproterenol) that increase intracellular levels of cAMP, results in the apoptotic death of most or all of the resting B cells. Conversely, treating cells with immobilized anti-immunoglobulin and interleukin 4, conditions known to prime cells, protects them from class II-mediated death and specifically from increases in nucleosomal fragments characteristic of apoptotic death. Freshly ex vivo activated B cells likewise are refractory to class II-mediated apoptosis. Treating B cells with anti-class II reagents causes an elevation of cAMP in resting, but not in activated, B cells. These results suggest that apoptotic death is a mechanism of prevention of nonspecific B-cell activation in the event that T-cell receptor and/or CD4 ligation of major histocompatibility complex class II occurs in the absence of antigen.
Newell
M K
MK
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
VanderWall
J
J
Beard
K S
KS
Freed
J H
JH
D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D002469:Cell Separation; D000242:Cyclic AMP / Q000378:metabolism; D004249:DNA Damage; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008806:Mice, Inbred AKR; D011940:Receptor Aggregation; D015398:Signal Transduction
D000949:Histocompatibility Antigens Class II; D000242:Cyclic AMP