Immunoglobulin gene

Immunoglobulin genes are a set of genes that encode antibodies or immunoglobulins, which are critical components of the immune system. These genes undergo a unique process of recombination, somatic hypermutation, and class switching to generate the vast diversity of antibodies necessary to recognize and neutralize an almost infinite variety of antigens.

Structure and Organization

Immunoglobulin genes are organized into three main loci in the genome: the heavy chain (IGH), kappa light chain (IGK), and lambda light chain (IGL) loci. Each locus consists of multiple variable (V), diversity (D), and joining (J) gene segments, along with constant (C) region genes that define the antibody's isotype.

Heavy Chain (IGH)

The IGH locus is located on chromosome 14 and contains multiple V, D, J, and C gene segments. During B cell development, one V, one D, and one J segment are randomly selected and recombined to form a functional VDJ exon that encodes the variable region of the heavy chain. The choice of C gene segment through class switch recombination determines the antibody isotype (e.g., IgM, IgG, IgA).

Light Chains (IGK and IGL)

The IGK locus on chromosome 2 and the IGL locus on chromosome 22 encode the kappa and lambda light chains, respectively. Each locus contains V, J, and C gene segments but lacks D segments. A V and J segment are recombined to form the variable region of the light chain.

Recombination and Diversity

The generation of antibody diversity is primarily achieved through V(D)J recombination, a process mediated by the RAG1 and RAG2 enzymes. This recombination event is highly variable, with additional diversity introduced through the insertion and deletion of nucleotides at V-D and D-J junctions (junctional diversity).

Following antigen stimulation, B cells can further diversify their antibody genes through somatic hypermutation, which introduces point mutations into the V regions, and class switch recombination, which changes the antibody isotype without altering its antigen specificity.

Clinical Significance

Mutations or dysregulation in immunoglobulin genes can lead to various immune system disorders, including immunodeficiencies, autoimmunity, and cancers such as multiple myeloma and certain types of lymphoma. Additionally, understanding the mechanisms of antibody diversity has been crucial in the development of antibody-based therapies and vaccines.

See Also

• Antibody
• B cell
• Immune system
• V(D)J recombination