Immunoglobulin kappa locus (IGK)

The Immunoglobulin kappa locus (IGK), located on human chromosome 2p11.2, is the genetic region responsible for encoding the kappa light chain of immunoglobulin molecules (NCBI Gene: 3514; HGNC: 5710). During B-cell maturation, this locus undergoes V(D)J recombination to produce a functional light chain, which then pairs with a heavy chain to form a complete antibody or B-cell receptor (BCR) (Janeway's Immunobiology, 9th ed.). In healthy individuals, B-cells express either a kappa or a lambda light chain, but not both, a phenomenon known as allelic exclusion. This distinction is clinically significant in oncology; B-cell malignancies such as multiple myeloma and various lymphomas are typically monoclonal, expressing only one type of light chain (Mayo Clinic Proceedings, 2005, PubMed: 15930486). Consequently, the kappa light chain serves as both a diagnostic biomarker (via the kappa/lambda ratio) and a therapeutic target for specialized treatments like kappa-directed CAR-T cells. These therapies, such as ICAR-14, aim to deplete malignant kappa-positive cells while preserving lambda-positive B-cells to maintain some immune function (Blood, 2015, PubMed: 26034296). This approach offers a more selective alternative to pan-B-cell targets like CD19 or CD20, potentially reducing the severity of treatment-induced immunodeficiency.

Other names

IGK@Kappa light chain locusImmunoglobulin kappa constantIGKCIGKVIGKJ

Targeted elimination of B-cells expressing the kappa light chain via CAR-T cell-mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC).