Endotoxin unresponsiveness in C3H/HEJ mice

Splenic lymphocytes from C3H/HeJ mice proliferate poorly in vitro when stimulated by certain B cell mitogens such as E. coli K235 endotoxin (LPS). In contrast, high responses are obtained from the C3H/HeN strain which is closely related as demonstrated by the absence of a measurable graft versus host or mixed lymphocyte reaction and survival of reciprocal skin grafts. Using these strains the authors have investigated the cellular defect in HeJ unresponsiveness. There is no evidence for absence of a critical helper cell since no cell type (T cells, B cells, macrophages) from the HeN (responder) strain could convey responsiveness to cultured HeJ spleen cells. Conversely, unresponsiveness was not due to the presence of a suppressor cell since removal of T cells or macrophages did not restore the response of the HeJ spleen cells. Furthermore no HeJ cell type was able to suppress the HeN response. Therefore, the direct effect of LPS on HeJ B cells was analyzed. It was found that another B cell mitogen, polyinosinic acid could stimulate HeJ proliferation. However, while this B cell mitogen response could be enhanced by addition of LPS to HeN spleen cells, LPS suppressed the response in HeJ spleen cells. It was therefore concluded that LPS unresponsiveness in HeJ mice is a direct result of an abnormal B cell LPS interaction.