Immunoglobulin lambda variable 3-21 (R110 mutant) B-cell receptor (IGLV3-21^R110^ BCR)

The Immunoglobulin lambda variable 3-21 (R110 mutant) B-cell receptor is a pathogenic variant of the B-cell receptor (BCR) expressed on the surface of malignant B-cells in a specific, aggressive subset of Chronic Lymphocytic Leukemia (CLL) (Stamatopoulos et al., 2018, Blood). This receptor is defined by a point mutation or junctional recruitment resulting in an Arginine residue at position 110 (R110) of the IGLV3-21 light chain (Minici et al., 2017, Nature Communications). Unlike conventional BCRs that require external antigen binding to initiate signaling, the IGLV3-21^R110^ BCR undergoes homotypic (self-to-self) interactions where the R110 residue of one BCR binds to the framework region of another (Dühren-von Minden et al., 2012, Nature). This interaction leads to autonomous, constitutive activation of the BCR signaling pathway, driving the proliferation and survival of CLL cells (Ghiotto et al., 2016, Leukemia). Clinically, the presence of this mutant receptor is a potent independent marker of poor prognosis, often associated with shorter time-to-first-treatment and reduced overall survival (Nadeu et al., 2021, Blood). While current treatments primarily utilize downstream inhibitors like Bruton's tyrosine kinase (BTK) inhibitors (e.g., ibrutinib), the unique structural interface created by the R110 mutation represents a potential target for highly specific therapeutic antibodies or small molecules designed to disrupt autonomous signaling (Maity et al., 2020, J Exp Med).

Other names

IGLV3-21*01 B-cell receptorR110-mutated IGLV3-21 BCRAutonomous B-cell receptorIGLV3-21-containing BCR

Inhibition of Bruton's tyrosine kinase (BTK), inhibition of phosphoinositide 3-kinase (PI3K), inhibition of B-cell lymphoma 2 (BCL-2), and experimental disruption of homotypic BCR-BCR interaction.