Talk about Immunoglobulin M

Immunoglobulin M (IgM) is one of several antibody isotypes (also known as immunoglobulins) produced by vertebrates.IgM is the largest antibody and it is the first antibody to appear in response to initial exposure to antigen.In humans and other mammals studied, plasmablasts present in the spleen are the main source of specific IgM production.In 1937, an antibody was observed in horses hyperimmunized with pneumococcal polysaccharide, which was much larger in size than the typical rabbit γ-globulin with a molecular weight of 990,000 Daltons.Based on its larger size, the new antibody was initially called gamma-macroglobulin and later IgM-M, for "macroglobulin."The V domains of normal immunoglobulins are highly heterogeneous, reflecting their role in defense against a variety of infectious microorganisms, and this heterogeneity hinders detailed structural analysis of IgM.Two homogeneous sources of IgM were subsequently discovered.First, the high molecular weight protein produced by some multiple myeloma patients is thought to be tumor-produced γ-macroglobulin, and since the tumor is clonal, the IgM it produces is homogeneous.In the 1960s, methods were developed to induce immunoglobulin-producing tumors (plasmacytomas) in mice, thereby providing a homogenous source of immunoglobulins of various isotypes, including IgM.More recently, expression of engineered immunoglobulin genes in tissue culture can be used to generate IgM with specific alterations, thereby determining the molecular requirements for traits of interest.

Structure

Immunoglobulins are composed of light and heavy chains.A light chain (λ or κ) is a protein of approximately 220 amino acids consisting of a variable domain VL (a segment of approximately 110 amino acids) and a constant domain CL (also approximately 110 amino acids long).The μ heavy chain of IgM is a protein of approximately 576 amino acids consisting of a variable domain (VH approximately 110 amino acids), four distinct constant region domains (Cμ1, Cμ2, Cμ3, Cμ4, each approximately 110 amino acids) and a "tail" of about 20 amino acids.The µ heavy chain bears oligosaccharides at five asparagine residues.Oligosaccharides on mouse and human IgM have been partially characterized by a variety of techniques including NMR, lectin binding, various chromatographic systems and enzyme sensitivities (for review see [9]). The oligosaccharide structures at each site varied in detail, and the major oligosaccharides biantennary, triantennary, high mannose differed between sites.The multimeric structure of IgM,a "heterodimer" consisting of one light chain (denoted L) and one heavy chain (denoted µ).The heavy and light chains are held together by disulfide bonds (depicted as red triangles) and non-covalent interactions.The two µL units are linked by a disulfide bond in the Cµ2 domain; this (µL)2 structure is often referred to as an IgM "monomer" because it resembles that of immunoglobulin G (IgG) in some respects.Based on its sedimentation velocity and appearance in electron micrographs, it was deduced that IgM usually occurs as a "pentamer", a polymer composed of five "monomers" [(µL)2]5, originally represented and models in 1D, with disulfide bonds between the Cµ3 domains and between the tails.also showed that pentameric IgM includes a third protein, the J chain.The J chain (J stands for junction) was found to be a covalently bonded component of polymeric IgA and IgM.The J chain is a small (approximately 137 amino acids) acidic protein,the J chain connects the two µ chains via a disulfide bond involving a tail cysteine.