THE MURINE IGG1/IGE CLASS SWITCH PROGRAM

Immunoglobulin class switching is controlled by cytokines. Thus, interleukin-4 (IL-4) directs class switching to both IgG1 and IgE. Consistent with this are the results reported here on restriction endonuclease analysis of active and inactive alleles of the IgH locus in IgE-producing cells. In cells that were stimulated in vitro by lipopolysaccharide and IL-4 the silent alleles preferentially switched to gamma-1, whereas in cells that were stimulated by antigen in vivo both active and inactive alleles switched to epsilon. Thirty percent of the recombined switch regions (S(mu)/S(epsilon) contain S(gamma)1 sequences, which we interpret as footprints of a previous switch to gamma-1. Since this percentage is a minimum estimate, between 30% and 100% of switching to epsilon must occur sequentially via gamma-1.