Immunoglobulin lambda locus (IGL)

The Immunoglobulin lambda locus (IGL) is a genomic region on chromosome 22 that encodes the lambda light chain of antibodies [1]. It plays a critical role in the adaptive immune system by undergoing V(D)J recombination to produce a diverse repertoire of light chains [2]. These light chains pair with heavy chains to form functional immunoglobulins or B-cell receptors capable of recognizing a wide array of antigens [3]. In certain pathological conditions, such as AL amyloidosis, clonal plasma cells overproduce monoclonal lambda light chains that misfold and aggregate into toxic fibrils [4]. These fibrils deposit in vital organs like the heart and kidneys, leading to progressive organ failure and high mortality [4]. Therapeutic targeting of the IGL products involves monoclonal antibodies that specifically bind to misfolded light chains or amyloid deposits to promote their clearance [5]. Additionally, therapies targeting the underlying plasma cell clone, such as proteasome inhibitors or anti-CD38 antibodies, are used to reduce the production of these pathogenic light chains [3]. Monitoring the levels of free lambda light chains in the serum is essential for diagnosing and assessing the treatment response in these patients [4].

Other names

IGLIGL@Lambda light chainImmunoglobulin lambda light chainIGLC

Monoclonal antibodies like birtamimab and anselamimab bind to specific epitopes on misfolded lambda light chains or amyloid fibrils, facilitating their clearance by phagocytic cells and preventing further tissue deposition [4, 5].