Antibody-secreting cell responses in the mouse liver

To elucidate the origins of biliary IgA antibodies, we investigated the isotype and specificity of antibody-secreting cells (ASC) in the liver in comparison with the spleen and intestinal lamina propria of mice immunized by peroral or parenteral routes. The profile of specific IgM, IgG1, IgG2a, and IgA ASC in the liver resembled that of the spleen rather than the lamina propria, regardless of the route of immunization. Peroral immunization increased the proportion of specific IgA ASC in all three organs. However, liver mononuclear cells (MNC) contained a higher proportion of total IgA-secreting cells than spleen cells. After immunization, the number and proportion of B220+ B cells were increased in the liver but not in the spleen. Although the predominant isotype of Ig and specific antibody in bile in response to immunization by either route was IgA, IgM and IgG were clearly detectable. However, specific activities of biliary antibodies relative to total Ig isotype were generally higher than in serum. The predominance of IgA-secreting cells in the liver and the large amount of IgA secreted in the bile resemble the situation at other secretory sites of the mucosal immune system. However, specific antibody-secreting cells appear to accumulate in the liver promptly after immunization, regardless of isotype, and contribute locally produced antibodies to the bile.