Polyclonal activation of B lymphocytes by lipopolysaccharide requires macrophage-derived interleukin-1

Lipopolysaccharide (LPS) is a potent murine polyclonal B-cell activator which induces cellular proliferation and IgM secretion. The precise role of activated macrophages in the induction of LPS-dependent, B-cell responses has been unclear. Although early reports concluded that the LPS effect occurs independently of other cell types, other studies have suggested that adherent macrophages exert either potentiating or inhibitory effects. In the present study, B-cell mitogenesis and IgM production were measured in primary spleen cell cultures after removing adherent cells by a variety of experimental procedures. B-cell activation by LPS was found to be strictly dependent on the presence of adherent macrophages. Antibody neutralization and cytokine reconstitution studies demonstrated that macrophage-derived interleukin- (IL-1) is a necessary co-factor for LPS-induced polyclonal activation.