ImmunoglobulinGene

Immunoglobulin genes encode antibodies produced by B lymphocytes. Antibodies are composed of two heavy chains and two light chains (kappa or lambda). The immunoglobulin genes are organized in three loci: the heavy chain locus (IGH) and the light chain loci IGK and IGL. In humans, IGH is on chromosome 14, IGK on chromosome 2, and IGL on chromosome 22. Each locus contains multiple variable (V), diversity (D) and joining (J) segments, followed by constant (C) region genes that encode the antibody isotypes.

The heavy chain locus contains V, D and J segments arranged upstream of constant region genes that encode μ, δ, γ, ε, and α isotypes. Light chain loci contain V and J segments joined to a single C region gene for κ or λ. Rearrangement of these segments occurs during B cell development via V(D)J recombination, mediated by RAG1/2, creating diverse antigen-binding sites. TdT adds nucleotides at junctions, contributing junctional diversity.

After successful rearrangement, transcription and RNA processing yield either a membrane-bound B cell receptor or a secreted antibody. Allelic exclusion ensures that only one heavy and one light chain allele is expressed per B cell. Further diversification occurs after antigen exposure: class switch recombination (CSR) alters the antibody isotype without changing specificity, driven by activation-induced cytidine deaminase (AID); and somatic hypermutation (SHM) introduces mutations in variable regions to increase affinity.