Mice refractory to lipopolysaccharide manifest high immunoglobulin A responses to orally administered antigen.

Lipid A-nonresponding C3H/HeJ mice manifested high immune responses to orally administered (either by feeding or by intragastric immunization) heterologous erythrocytes when compared with syngeneic lipid A-responding C3H/HeN mice. Prolonged consumption of horse erythrocytes resulted in a significant secretory immune response in both C3H mouse strains as evidenced by high salivary agglutinin titers. Although salivary agglutinin titers were only slightly greater in C3H/HeJ mice than those of C3H/HeN mice, serum agglutinin titers and immunoglobulin A (IgA) levels were consistently higher (two- to fourfold) in C3H/HeJ mice. The appearance of anti-horse erythrocyte plaque-forming cell responses in spleens of immunized animals was followed by an increase in salivary anti-horse erythrocyte agglutinin activity. Peak levels of both responses were attained after approximately 3 weeks of immunization. Differences in immune responsiveness between C3H mouse strains were also evident at the cellular level since splenic IgA anti-horse erythrocyte plaque-forming cell responses in fed C3H/HeJ mice were twofold higher than those in similarly treated C3H/HeN mice. This higher response pattern was also observed when C3H/HeJ mice manifested threefold higher splenic IgM and IgA plaque-forming cell responses to intragastrically administered sheep erythrocytes. Thus, higher responsiveness was observed in the C3H/HeJ mice given heterologous erythrocytes by the oral route. Furthermore, levels of serum IgA in 10- to 12-month-old nonimmunized C3H/HeJ mice were higher than those of C3H/HeN mice. These findings suggest that lack of host responsiveness to lipopolysaccharide affects the manifestation of subsequent immune responses to orally administered antigens. The possible mechanisms and implications of this high responsiveness are discussed.