Igk, also known as immunoglobulin kappa locus, is a crucial gene involved in the development of B cells. In developing B cells, it undergoes V(D)J recombination to assemble exons encoding Igκ variable regions from gene segments clustered across the Igk locus. This recombination is essential for the generation of diverse antibodies, which are key components of the adaptive immune response [1].

Research shows that Igk undergoes robust primary and secondary rearrangements, and RAG scanning from the primary Jκ -RC terminates within the CTCF -site -based Sis element. Igk seems to have evolved strong RSSs to mediate diffusional Vκ -to -Jκ joining [1]. Also, inactivation of the NF -κB essential modulator (Nemo) protein in mouse pre -B cells, an effector of ATM signaling, diminishes RAG DSB -triggered repression of Rag1/Rag2 transcription and Igk accessibility, increasing the frequency of B cells expressing Igκ proteins from both alleles, indicating Nemo -dependent, ATM -mediated signals enforce Igκ allelic exclusion [2].

In conclusion, Igk is vital for antibody diversity generation through V(D)J recombination in B cells. Mouse models, especially those with Nemo inactivation, have been instrumental in revealing the mechanisms underlying Igκ allelic exclusion. Understanding Igk's function provides insights into the normal development of the immune system and may have implications for diseases related to abnormal B -cell development and antibody production.

References:

1. Zhang, Yiwen, Li, Xiang, Ba, Zhaoqing, Alt, Frederick W, Hu, Hongli. 2024. Molecular basis for differential Igk versus Igh V(D)J joining mechanisms. In Nature, 630, 189-197. doi:10.1038/s41586-024-07477-y. https://pubmed.ncbi.nlm.nih.gov/38811728/

2. Glynn, Rebecca A, Bassing, Craig H. 2021. Nemo-Dependent, ATM-Mediated Signals from RAG DNA Breaks at Igk Feedback Inhibit V κ Recombination to Enforce Igκ Allelic Exclusion. In Journal of immunology (Baltimore, Md. : 1950), 208, 371-383. doi:10.4049/jimmunol.2100696. https://pubmed.ncbi.nlm.nih.gov/34965965/