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Turnover and Shedding of Ia Antigens by Murine Spleen Cells in Culture¹

Departments of Cell Biology, Pathology (Immunology) and Surgery, Yale University School of Medicine, New Haven, Connecticut 06510

Abstract

Lactoperoxidase-catalyzed radioiodination was used to examine the metabolic fate of surface Ia antigens on murine spleen cells in culture. Ia antigens, detected predominately on splenic B lymphocytes, were lost from the cultured cells with biphasic kinetics: a 4 to 6 hr rapid phase, t = 5 hr followed by slow release through 20 hr, t = 30 hr. The rapid loss of Ia antigens observed was abolished by both harsh iodination conditions and nonphysiologic incubation conditions. The rapid decline in Ia activity was shown to be due to shedding of intact Ia antigens from the cell and to a predominant release of IA subregion-coded proteins. Release of Ia antigens from the cell was accomplished by replacement at the cell surface, and thus reflected net membrane Ia turnover. Ia shedding was shown to be extremely temperature dependent, reflecting both a comparatively high activation enthalpy and entropy requirement for turnover.

Footnotes

¹ Supported by United States Public Health Service National Institutes of Health Grants CA14216, AI12577, and GM07205.

² SGE is a predoctoral fellow of the Medical Scientist Training Program, NIH, and is supported in part by an Upjohn Graduate Fellow Research Award.

³ To whom correspondence should be addressed.

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