Mice Refractory to Lipopolysaccharide Manifest High Immunoglobulin A Responses to Orally Administered Antigen

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Abstract
Lipid A-nonresponding C3H/HeJ mice manifested high immune responses to orally administered (by feeding or by intragastric immunization) heterologous erythrocytes compared to syngeneic lipid A-responding C3H/HeN mice. Prolonged consumption of horse erythrocytes resulted in a significant secretory immune response in both C3H mouse strains, 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 IgA levels were consistently higher (2- to 4-fold) 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 responses were attained after .apprx. 3 wk of immunization. Differences in immune responsiveness between C3H mouse strains were evident at the cellular level since splenic IgA anti-horse erythrocyte plaque-forming cell responses in fed C3H/HeJ mice were 2-fold higher than those in similarly treated C3H/HeN mice. This higher response pattern was observed when C3H/HeJ mice manifested 3-fold higher splenic IgM and IgA plaque-forming cell responses to intragastrically administered sheep erythrocytes. Higher responsiveness was observed in the C3H/HeJ mice given heterologous erythrocytes by the oral route. Levels of serum IgA in 10-12 mo. old nonimmunized C3H/HeJ mice were higher than those of C3H/HeN mice. Lack of host responsiveness to lipopolysaccharide affects the manifestation of subsequent immune response to orally administered antigens. The possible mechanisms and implications of this high responsiveness are discussed.