Recombination in the Human IGK Locus

The human IGK locus is probably the most complex of all antigen-receptor loci because of the presence of many elements that can be involved in V(D)J recombination. Next to classical Vkappa-Jkappa recombinations and deletional recombinations involving Kde (intron-Kde, Vkappa-Kde), JkappaRSS-intronRSS signal joints and Vkappa-intronRSS and JkappaRSS-Kde pseudohybrid joints are observed in human B-cell malignancies and also in normal human B cells. These recombinations occur in an ordered and tightly regulated way. Although DNA (de)methylation, histone (de)acetylation, and nuclear positioning all play a role in this regulation, much is still to be learned about the exact factors involved. One of these factors seems to be E2A that is known to be important in B-cell development and has a direct role in the induction of human endogenous IGK recombination. Contrary to the human IGH locus, aberrant recombinations resulting in chromosomal translocations are not very frequent in the human IGK locus. Despite this, IGK recombinations have diagnostic and clinical implications, being important PCR targets for clonality and MRD studies.