title: Effect of gamma radiation on resting B lymphocytes. II. Functional characterization of the antigen-presentation defect.
abstract: The effect of radiation on three discrete Ag-presentation functions in resting B cells was examined: 1) Ag uptake and processing, 2) expression of processed Ag in the context of functional class II molecules, and 3) provision of necessary co-stimulatory, or "second," signals. Analysis of radiation's effect on B cell presentation of intact vs fragmented Ag or its effect on presentation by Ag-pulsed B cells indicated that damage to Ag uptake and processing could not account for the bulk of the radiation-induced Ag-presentation defect. Experiments with phosphatidylinositol hydrolysis as an indirect measure of TCR occupancy suggested that irradiation caused a fairly rapid (within 1 to 2 h) decrease in the ability of the B cell APC to display a stimulatory combination of Ag and class II molecule. Ag dose-response analyses demonstrated that when presenting a fragment of the Ag pigeon cytochrome c to a T cell clone, 3000 rad-treated B cell APC were able to stimulate approximately 50% as much phosphatidylinositol turnover as unirradiated B cells. It was also found that, in contrast to their inability to initiate T cell proliferation, and similarly to chemically cross-linked splenocytes, heavily irradiated resting B cells plus Ag induced a state of Ag hyporesponsiveness in T cell clones. This effect on T cells had the same Ag- and MHC-specificity as did receptor occupancy required for proliferation, indicating that heavily irradiated resting B cells bear functional class II molecules. Co-culture of T cells with allogeneic B cells and syngeneic heavily irradiated B cells or chemically cross-linked splenic APC plus Ag resulted in T cell proliferation and interfered with the induction of the hyporesponsive state. This co-stimulatory function was radiosensitive in resting allogeneic B cells. Together, these data support the hypothesis that the major functional consequences of radiation to resting B cell APC are a reduction in the effective display of Ag plus class II molecules and, probably what is more important, a loss in the ability to provide APC-derived co-stimulatory signals.
authors.affiliation: Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.
authors.forename: J D
authors.initials: JD
authors.lastname: Ashwell
authors.forename: M K
authors.initials: MK
authors.lastname: Jenkins
authors.forename: R H
authors.initials: RH
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000528:radiation effects*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D002999:Clone Cells / Q000276:immunology; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D007108:Immune Tolerance / Q000528:radiation effects; D007399:Interphase / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D003574:Cytochrome c Group; D011948:Receptors, Antigen, T-Cell