IL-4 induces the specific rearrangement of γ1 genes on the expressed and unexpressed chromosomes of lipopolysaccharide-activated normal murine B cells

Small, resting, surface IgM⁺/surface IgD⁺ murine B cells undergo an Ig class switch to IgG₁ or IgE after stimulation with LPS and T cell supernatants containing IL-4. To firmly establish the role of IL-4 in the directed switch recombination observed in IgG₁-secreting cells, we have 1) used highly purified native IL-4 instead of T cell supernatants, 2) used resting B cells from F₁ mice in which the active IgH allele was determined before culture, 3) taken advantage of the allelic differences in the restriction fragment lengths of μ, γ1, γ2b, and γ3 loci to determine the status of the C(H) genes on both the expressed and unexpressed chromosomes, and 4) used different restriction enzymes to distinguish between deletion and rearrangement of a given C(H) gene. Our results indicate that LPS alone induces rearrangement of the γ3 genes on both chromosomes wheras stimulation with LPS plus IL-4 results in deletion of γ3 genes and rearrangement of γ1 genes on both chromosomes. The studies definitively establish the role of IL-4 in directed switch recombination to the γ1 locus in LPS-stimulated murine B cells.