Mitogenic activity of bacterial lipopolysaccharides in vivo: morphological and functional characterization of responding cells

Abstract

The in vivo effect of bacterial lipopolysaccharides (LPS) on mouse spleen cell subpopulations was investigated. Intravenous administration of LPS resulted in marked enlargement of the spleen, accompanied by increased cellular proliferation and enhanced nucleated cell recoveries. At least two morphologically distinct cell types appeared to be targets for LPS. Polymorphonuclear leukocytes accumulated rapidly with a relatively minor degree of cell division. In contrast, a substantial proportion of splenic lymphocytes transformed into large lymphocytes and blast cells which actively incorporated [3H]thymidine. Proliferating cells were identified as bone marrow-derived (B) lymphocytes by their ability to form C3-dependent rosettes and to synthesize immunoglobulin. These cellular responses were not antigenically induced, since LPS derived from mutants lacking the polysaccharide moiety gave similar results. Thus, splenic B lymphocytes appear to interact and respond to LPS in vivo in the same manner as observed in vitro. These data suggest that the capacity of LPS to directly activate B lymphocytes, initiate cellular proliferation, and induce immunoglobulin production by bone marrow-derived cells in vivo may contribute to its adjuvant activity.