Effect of ethanol on B cell expression of major histocompatibility class II proteins in immunized mice.
Acute or chronic exposure to ethanol (EtOH), as well as other stimuli that induce a neuroendocrine stress response, can decrease the expression of MHC class II proteins (immune-associated antigens, Ia) on B cells and macrophages. In a mouse model for binge drinking, it has been shown that this decrease is caused by EtOH-induced increases in endogenous glucocorticoids. Decreased Ia expression would be expected to suppress T-dependent humoral responses, and such suppression has been noted in our model. However, it has been reported that activated B cells are much less susceptible to glucocorticoid-induced decreases in Ia expression than are resting B cells. Thus, it is not clear that the decreased Ia observed in our previous studies with non-immunized mice could account for decreased humoral responses, because it has not been directly determined that decreased Ia expression occurs in immunized mice. To examine this issue, splenocytes from mice immunized with sheep erythrocytes were studied by flow cytometry. Mice were treated with EtOH by gavage and immunized 12 h later, because our previous results indicate that this produces maximal suppression of the humoral response. In immunized mice, EtOH decreased Ia expression on B cells at 6 and 12 h after immunization, but not at 24 or 74 h. In a dose-response study, a substantial decrease in Ia expression on B cells was observed at an EtOH dosage of 6.0 or 7.0 g/kg. Thus, decreased Ia expression is a potential mechanism for EtOH-induced suppression of the humoral response. A glucocorticoid antagonist (RU 486) partially blocked the EtOH-induced decrease in Ia expression, suggesting that glucocorticoids are involved in the reduction of Ia expression in immunized mice. Direct administration of corticosterone to produce blood levels comparable to those noted in EtOH-treated mice did not significantly decrease Ia expression, but Ia expression tended to be lower in mice treated with corticosterone. Taken together, these results indicate that glucocorticoids play some role in decreasing Ia expression in immunized mice, but they are less important than in non-immunized mice.
Department of Biological Sciences, Mississippi State University, Mississippi 39762, USA.
P A
PA
Weiss
S D
SD
Collier
S B
SB
Pruett
D000428:Alcohol Drinking / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004912:Erythrocytes / Q000276:immunology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012756:Sheep; D013154:Spleen / Q000166:cytology / Q000276:immunology
D002492:Central Nervous System Depressants; D005938:Glucocorticoids; D000949:Histocompatibility Antigens Class II; D000431:Ethanol