Antigen receptor loci are organized into variable (V), diversity (D) and joining (J) gene segments that rearrange to generate antigen receptor repertoires. Here, we identified an enhancer (E34) in the murine immunoglobulin kappa (Igk) locus that instructed rearrangement of Vκgenes located in a sub-topologically associating domain, including a Vκgene encoding for antibodies targeting bacterial phosphorylcholine. We show that E34 instructs the nuclear repositioning of the E34 sub-topologically associating domain from a recombination-repressive compartment to a recombination-permissive compartment that is marked by equivalent activating histone modifications. Finally, we found that E34-instructed Vκ-Jκrearrangement was essential to combat Streptococcus pneumoniaebut not methicillin-resistant Staphylococcus aureusor influenza infections. We propose that the merging of Vκgenes with Jκelements is instructed by one-dimensional epigenetic information imposed by enhancers across Vκand Jκgenomic regions. The data also reveal how enhancers generate distinct antibody repertoires that provide protection against lethal bacterial infection.