Heterologous desensitization of the high affinity receptor for IgE (Fc epsilon R1) on RBL cells.
To study the properties of Fc epsilon RI desensitization induced by aggregation of that receptor, RBL cells were sensitized with a mixture of two different IgE mAb to create two different populations of IgE-receptor complexes. Cross-linking of one receptor population containing anti-dinitrophenyl (DNP) IgE with a bivalent Ag, 1-DNP-amino-12-biotinamidododecane)2-avidin ((DNP)2-avidin), results in desensitization of a subsequent response, both of the same receptor population (homologous desensitization) and of the second receptor population containing anti-5-dimethylaminonaphthalene-1-sulfonyl (dansyl) IgE (heterologous desensitization). The extent of heterologous desensitization is dependent on several parameters, including the concentration of both the first and the second Ag and the densities of the respective IgE populations. Heterologous desensitization of the Ca2+ response is more sensitive to the concentration of the second stimulus (dansyl-BSA) than heterologous desensitization of the degranulation response. AlF4-, which activates GTP-binding proteins, can effectively replace (DNP)2-avidin as the initial stimulant and desensitizing agent. Other agents that mobilize intracellular Ca2+ including thrombin and a Ca2+ ionophore are less effective at replacing (DNP)2-avidin. Because prestimulation with Ag does not desensitize subsequent responses to AlF4- or Ca2+ ionophore, it appears that signal transduction via Fc epsilon RI is impaired at an early step. Addition of monovalent DNP hapten within approximately 10 min after cross-linking by (DNP)2-avidin completely prevents the desensitization of the subsequent Ca2+ or degranulation response to dansyl-BSA. After longer times of incubation with DNP Ag, the DNP hapten becomes increasingly less effective at preventing the desensitization of the dansyl-BSA response, even though ongoing signal transduction by the DNP Ag is halted. These results suggest a form of cellular memory for the desensitized state.
Weetall
M
M
Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, NY 14853-1301.
Holowka
D
D
Baird
B
B
D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation; D002460:Cell Line; D004136:Dinitrobenzenes / Q000276:immunology; D005459:Fluorides; D005461:Fluorine / Q000494:pharmacology; D007073:Immunoglobulin E / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051381:Rats; D017455:Receptors, IgE / Q000502:physiology*; D015398:Signal Transduction
D017607:Aluminum Compounds; D004136:Dinitrobenzenes; D017455:Receptors, IgE; C050992:tetrafluoroaluminate; D005461:Fluorine; D007073:Immunoglobulin E; D000535:Aluminum; D005459:Fluorides; D002118:Calcium