Absence of lipopolysaccharide high-dose paralysis in B-cell responses: Implications for the one-signal theory

Abstract

Over 20 years ago, Coutinho and Moller reported that high concentrations of LPS were paralytic for the development of antibody secreting cells (ASC). This data was used to explain bell-shaped dose-response curves observed for antihapten antibody formation in response to haptenated LPS. In turn, this bell curve was used to formulate the one-signal model of B cell activation, which argued that antigen signalling was generally unimportant to B cell responses. The present paper re-examines LPS dose-response curves and finds results that do not support the view that high doses of LPS inhibit B cell differentiation to ASC. If high-dose paralysis is not an attribute of LPS stimulation, then the bell-shaped dose curve for hapten-specific ASC originally observed by Coutinho and Moller required an alternative explanation. Through the use of haptenated Ficoll, it was possible to show that the generation of LPS-induced antitrinitrophenol ASC could be inhibited by antigen presented on an inert substrate. Thus, the transmission of surface Ig-mediated (antigen) signals at higher concentrations can explain the antihapten bell-shaped dose curves, in contradiction to the conclusions of the one-signal model.