Recombination-center ablation of Igh and Igκ defines distinct developmental and immune phenotypes in mice

Genetic disruption of immunoglobulin loci has long established the requirement for heavy- and light-chain rearrangement during B-cell development. Here, we generated Igh -KO, Igκ -KO, and Igh/Igκ double-KO mice by CRISPR/Cas9-mediated deletion of essential recombination-center elements and performed a coordinated side-by-side phenotypic analysis. Consistent with established heavy-chain-deficient models, Igh ablation caused a profound block in B-cell development beyond the pro-B stage, with marked loss of peripheral B cells and humoral effector populations. Consistent with classic Igκ -targeting studies, Igκ ablation permitted substantial B-cell development through compensatory Igλ usage. Within this matched experimental framework, Igκ -deficient mice also showed altered splenic and peritoneal B-cell subset composition, whereas Igh -deficient mice showed reduced splenic and thymic T-cell numbers, reduced Foxp3 + regulatory T-cell abundance, and altered secondary lymphoid-tissue organization. Together, the three mutant lines provide a comparative genetic resource and phenotypic reference for assessing the consequences of defined Igh and Igκ lesions across multiple immune compartments.