Cellular mechanism of endotoxin unresponsiveness in C3H/HeJ mice.
B cells from C3H/HeJ mice fail to respond to an endotoxin (LPS K235) which is mitogenic for normal mice including the closely related C3H/HeN strain. The cellular basis for this unresponsive state has been investigated. The C3H/HeJ mice have normal numbers of B cells, which are capable of normal responses to other B cell mitogens, such as polyinosinic acid (Poly I). Addition of normal macrophages or spleen cells fails to reconstitute the normal response. Furthermore, neither macrophages nor spleen cells from the C3H/HeJ strain suppress the normal C3H/HeN spleen cells. Finally, spleen cells enriched for B cells by the removal of macrophages or T cells demonstrate the same differences in responsiveness to LPS. These results indicate that LPS unresponsiveness is a defect of the B cell itself and not due to suppressor cells or the absence of helper cells. When LPS is added to Poly I-stimulated cultures, there is additional enhancement of the response of normal C3H/HeN spleen cells. However, LPS causes a dose-dependent suppression of the Poly I response of C3H/HeJ spleen cells. This suppression is dependent on the time of addition of LPS to the Poly I-stimulated cultures. These data are interpreted as indicating that the binding of LPS to the membrane of C3H/HeJ B cells results in their inactivation or suppression, and that this is the basis of LPS unresponsiveness in this mouse strain.
D000818:Animals; D001402:B-Lymphocytes; D002452:Cell Count; D002470:Cell Survival; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005260:Female; D007111:Immunity, Cellular; D008070:Lipopolysaccharides / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D011069:Poly I / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013154:Spleen / Q000166:cytology
D004731:Endotoxins; D008070:Lipopolysaccharides; D011069:Poly I