How cytokines control immunoglobulin class switching.

B lymphocytes can alter the class of antibody they produce by immunoglobulin class switch recombination. This recombination is targeted by distinct cytokines to particular switch regions. Prior to switch recombination, the same cytokines induce transcription through the targeted switch regions and generate IH "switch" transcripts. To show whether the two events are functionally related, we have replaced the endogenous interleukin-4 (IL-4) dependent promoter of murine I gamma 1 switch transcripts by an heterologous promoter, the human metallothionein IIA (hMT) promoter. Indeed, switch recombination can be targeted to IgG1 by the hMT promoter. In mutant mice, which cannot generate processed switch transcripts, switch recombination cannot be targeted to IgG1 by the hMT promoter. Thus, IL-4 targets switch recombination to IgG1 by induction of processed switch transcripts.