Immunoglobulin heavy locus, also known as IGH, is a region on human
chromosome 14 that contains a
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
for the
heavy chains of human
antibodies
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...
(or immunoglobulins).
Immunoglobulins recognize foreign antigens and initiate immune responses such as
phagocytosis
Phagocytosis () is the process by which a cell (biology), cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs ph ...
and the complement system. Each immunoglobulin molecule consists of two identical heavy chains and two identical light chains. This region represents the germline organization of the heavy chain locus. The locus includes V (variable), D (diversity), J (joining), and C (constant) segments. During
B cell development,
a recombination event at the DNA level joins a single D segment with a J segment; the fused D-J exon of this partially rearranged D-J region is then joined to a V segment. The rearranged V-D-J region containing a fused V-D-J exon is then transcribed and fused at the RNA level to the IGHM constant region; this transcript encodes a mu heavy chain. Later in development B cells generate V-D-J-Cmu-Cdelta pre-messenger RNA, which is alternatively spliced to encode either a mu or a delta heavy chain. Mature B cells in the lymph nodes undergo
switch recombination, so that the fused V-D-J gene segment is brought in proximity to one of the IGHG, IGHA, or IGHE gene segments and each cell expresses either the gamma, alpha, or epsilon heavy chain. Potential recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random addition of nucleotides by
terminal deoxynucleotidyl transferase
Terminal deoxynucleotidyl transferase (TdT), also known as DNA nucleotidylexotransferase (DNTT) or terminal transferase, is a specialized DNA polymerase expressed in immature, pre-B, pre-T lymphoid cells, and acute lymphoblastic leukemia/lymphom ...
, and by
somatic hypermutation
Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes). A major component of the process of affinity maturation, SHM diversifies B cell receptors used t ...
, which occurs during B cell maturation in the spleen and lymph nodes. Several V, D, J, and C segments are known to be incapable of encoding a protein and are considered pseudogenous gene segments (often simply referred to as pseudogenes).
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Nomenclature
Symbols for variable (V) immunoglobulin gene segments start with IGHV and include two or three numbers separated by dashes. Examples:
:IGHV1-2, IGHV1-3, …, IGHV1-69-2, IGHV2-5, …, IGHV7-4-1
Symbols for diversity (D) immunoglobulin gene segments start with IGHD and include two numbers separated by dashes. Examples:
:IGHD1-1, IGHD1-7, …, IGHD7-27
Symbols for joining (J) immunoglobulin gene segments:
:IGHJ1, IGHJ2, IGHJ3, IGHJ4, IGHJ5, IGHJ6
Symbols for constant region (C) immunoglobulin genes:
:Heavy chain alpha ( IgA): IGHA1, IGHA2
:Heavy chain gamma ( IgG): IGHG1, IGHG2, IGHG3, IGHG4
:Heavy chain delta ( IgD): IGHD
:Heavy chain epsilon ( IgE): IGHE
:Heavy chain mu ( IgM): IGHM
See also
* IGHV@
References
Further reading
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Antibodies
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