CIRCULAR DNA IS EXCISED BY IMMUNOGLOBULIN CLASS SWITCH RECOMBINATION

We have purified extrachromosomal circular DNAs from adult mouse spleen cells, and cloned into a phage vector the BamHl fragments hybridizing with Cμ and Sγ1 probes. We obtained 52 Sμ+Sγ1+ clones by screening 1.4 million phage clones derived from spleen cells stimulated with bacterial lipopolysaccharide and interleukin 4. We have identified the breakpoints of six clones that contain Sγ1 and Sμ sequences fused in the 5′ to 3′ orientation. All these switch recombination sites were assigned to the central repetitive sequences of the Sμ and Sγ1 regions. Since the common Sμ-Sγ1 sequences at the recombination sites are at most 2 bases long, typical homologous recombination cannot account for their joining. These findings provide direct evidence that μ-γ1 class switching can occur by the looping out and excision of chromosomal DNA, with formation of a circle. © 1990.