Opposite Effects of BCG on Spleen and Lymph Node Cells: Lymphocyte Proliferation and Immunoglobulin Synthesis

C57BL/6 mice were immunized intravenously (i.v.), intraperitoneally (i.p.), or subcutaneously with one dose of Bacillus Calmette-Guérin (BCG). At various time intervals after injection, the lymphocyte response, as measured by thymidine incorporation into DNA, and the number of immunoglobulin-secreting cells were determined in vitro before and after mitogenic stimulation with phytohemagglutinin, concanavalin A, or lipopolysaccharide. In unstimulated cultures, the spontaneous thymidine incorporation and immunoglobulin synthesis of spleen cells were increased to some extent in mice infected i.p. or i.v. with BCG, as compared with noninfected mice. In contrast, after mitogenic stimulation, a marked depression of the proliferative response of spleen cells to both T- and B-cell mitogens and a marked inhibition of LPS-induced immunoglobulin secretion were observed in mice infected i.v. and to a lesser extent in those infected i.p. The depression of lymphoblastogenesis in spleens was fully established 15 days after infection and persisted for a long period of time. When unfractionated or plastic-adherent spleen cells from BCG-infected mice were cultured with normal spleen cells, a strong depression of their reactivity to phytohemagglutinin, concanavalin A, and lipopolysaccharide was observed. After the removal of cells adherent to plastic, the response was partially restored in the nonadherent population from mice infected i.p., but not in that from mice infected i.v. After mitogenic stimulation, lymph node cells of mice inoculated subcutaneously showed a response to mitogen higher than that of normal cells. These results thus demonstrate that, depending on the route of administration, BCG exerts very different effects.