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Immunoglobulin genetics

Francisco A Bonilla, MD, PhD
Section Editor
Jennifer M Puck, MD
Deputy Editor
Anna M Feldweg, MD


The genetics of immunoglobulin (Ig) during both B cell development in the bone marrow and the induction of the humoral immune response are presented here. Discussions concerning B cell development and the humoral immune response are reviewed separately (see "Normal B and T lymphocyte development" and "The humoral immune response"). A website devoted to immunoglobulin genetics is available [1].


There are several classes of immunoglobulin (Ig) that are categorized by a unique heavy chain structure: IgG, IgM, IgA, IgD, and IgE. There are also subclasses of IgG (IgG1 to 4) and of IgA (IgA1,2) (see "Structure of immunoglobulins"). In addition, there are two different types of antibody light chains, kappa and lambda. Ig heavy chains and each type of light chain are encoded by genes in different loci. The table shows the locations of these gene complexes on human chromosomes (table 1).

Genes capable of encoding a complete antibody heavy or light chain do not exist, as such, within the DNA of most cells. The complete genes are assembled by the union of separate gene segments. These segments are widely separated in germ cells and in all somatic cells, except for B lymphocytes. Within B cells, these genes rearrange their relative positions to create a "mature" Ig gene that can encode a functional protein. This rearrangement process is the core of the immune system's ability to generate antibodies capable of recognizing the tremendous variety of antigenic structures in nature.

An Ig light chain gene is assembled from three types of gene segments. These are the light chain variable region (VL), joining region (JL), and constant region (CL) gene segments (figure 1). Similarly, heavy chain gene segments are VH, JH and CH, and another type of gene segment called D (diversity) (figure 2).

The nomenclature of the gene segments derives from names assigned to portions of antibody heavy or light chains based upon an analysis of their amino acid sequences (see "Structure of immunoglobulins"). Thus, the variable region shows great variation from one antibody chain to another. The constant region, as its name implies, is invariant within an Ig class or subclass. The joining and diversity regions were the names given to areas between V and C, each having its own characteristic sequence pattern. The variable regions of the heavy and light chains together form the antibody combining site. This is the portion of the Ig molecule that makes contact with antigen. (See "Function and clinical applications of immunoglobulins".)

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Literature review current through: Oct 2017. | This topic last updated: Feb 02, 2016.
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