IL-4 induces the specific rearrangement of gamma 1 genes on the expressed and unexpressed chromosomes of lipopolysaccharide-activated normal murine B cells

Abstract

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 mu, gamma 1, gamma 2b, and gamma 3 loci to determine the status of the CH genes on both the expressed and unexpressed chromosomes, and 4) used different restriction enzymes to distinguish between deletion and rearrangement of a given CH gene. Our results indicate that LPS alone induces rearrangement of the gamma 3 genes on both chromosomes whereas stimulation with LPS plus IL-4 results in deletion of gamma 3 genes and rearrangement of gamma 1 genes on both chromosomes. The studies definitively establish the role of IL-4 in directed switch recombination to the gamma 1 locus in LPS-stimulated murine B cells.