LightChains

Light chains are polypeptide components of immunoglobulins, existing as two types in humans: kappa (κ) and lambda (λ). They pair with heavy chains to form intact immunoglobulin molecules. Light chains contain a variable domain (VL) that participates in antigen binding and a constant domain (CL) that mediates effector interactions, connected by a flexible linker. The light chain is typically about 214 amino acids long and around 25 kilodaltons when unbound; disulfide bonds link the light and heavy chains within the antibody.

Genetics and rearrangement

Light chain genes are organized into distinct loci: κ on chromosome 2 and λ on chromosome 22. In developing B cells, V and J gene segments recombine (VJ rearrangement) to form a functional light chain exon, with multiple V and J segments contributing to diversity. Usually κ rearranges first; if unsuccessful, λ rearrangement occurs. Allelic exclusion ensures that each B cell expresses light chain from one chromosome, and typically only one light chain is produced per cell.

Expression and assembly

The expressed light chain is synthesized in the cytoplasm and assembles with a heavy chain in the endoplasmic reticulum to form a complete immunoglobulin. Ig molecules may be membrane-bound as B cell receptors or secreted as soluble antibodies. In most humans, about two-thirds of circulating light chains are κ, with λ making up the remainder.

Clinical significance

Free light chains (FLCs) are secreted by plasma cells and circulate in serum and urine. The serum κ to λ ratio is used to detect monoclonal gammopathies such as multiple myeloma and AL amyloidosis, and to monitor treatment response. Abnormal ratios or excess FLCs can indicate clonal plasma cell disorders even when traditional immunoglobulin levels are normal.