IgM (Immunoglobulin Mu Heavy Chain) (IGHM) Antibody – Mouse Monoclonal

Immunoglobulins (Ig) are the antigen recognition molecules of B cells. An Ig molecule is made up of 2 identical heavy chains and 2 identical light chains (see MIM 147200) joined by disulfide bonds so that each heavy chain is linked to a light chain and the 2 heavy chains are linked together. Each Ig heavy chain has an N-terminal variable (V) region containing the antigen-binding site and a C-terminal constant (C) region, encoded by an individual C region gene, that determines the isotype of the antibody and provides effector or signaling functions. The heavy chain V region is encoded by 1 each of 3 types of genes: V genes (see MIM 147070), joining (J) genes (see MIM 147010), and diversity (D) genes (see MIM 146910). The C region genes are clustered downstream of the V region genes within the heavy chain locus on chromosome 14. The IGHM gene encodes the C region of the mu heavy chain, which defines the IgM isotype. Naive B cells express the transmembrane forms of IgM and IgD (see IGHD; MIM 1471770) on their surface. During an antibody response, activated B cells can switch to the expression of individual downstream heavy chain C region genes by a process of somatic recombination known as isotype switching. In addition, secreted Ig forms that act as antibodies can be produced by alternative RNA processing of the heavy chain C region sequences. Although the membrane forms of all Ig isotypes are monomeric, secreted IgM forms pentamers, and occasionally hexamers, in plasma (summary by Janeway et al., 2005).[supplied by OMIM, Aug 2010]

IGHM: IgM antibodies play an important role in primary defense mechanisms. They have been shown to be involved in early recognition of external invaders like bacteria and viruses, cellular waste and modified self, as well as in recognition and elimination of precancerous and cancerous lesions. The membrane- bound form is found in the majority of normal B-cells alongside with IgD. Membrane-bound IgM induces the phosphorylation of CD79A and CD79B by the Src family of protein tyrosine kinases. It may cause death of cells by apoptosis. It is also found in soluble form, which represents about 30% of the total serum immunoglobulins where it is found almost exclusively as an homopentamer. After the antigen binds to the B-cell receptor, the secreted form is secreted in large amounts. Defects in IGHM are the cause of agammaglobulinemia type 1 (AGM1). It is a primary immunodeficiency characterized by profoundly low or absent serum antibodies and low or absent circulating B-cells due to an early block of B-cell development. Affected individuals develop severe infections in the first years of life. 2 isoforms of the human protein are produced by alternative splicing.

Chromosomal Location of Human Ortholog: 14q32.33

Cellular Component: cell surface; external side of plasma membrane; extracellular space; plasma membrane

Molecular Function: antigen binding; peptidoglycan binding; phosphatidylcholine binding; protein binding; single-stranded DNA binding

Biological Process: adaptive immune response; antibacterial humoral response; B cell receptor signaling pathway; complement activation, classical pathway; defense response to Gram-negative bacterium; innate immune response; phagocytosis, engulfment; phagocytosis, recognition; positive regulation of B cell activation

Disease: Agammaglobulinemia 1, Autosomal Recessive