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Immunoglobulin M

immunoglobulin m, immunoglobulin m high level
Immunoglobulin M IgM is one of several forms of antibody that are produced by vertebrates IgM is the largest antibody, and it is the first antibody to appear in the response to initial exposure to an antigen12 In the case of humans and other mammals that have been studied, the spleen, where plasmablasts responsible for antibody production reside, is the major site of specific IgM production34

Contents

  • 1 Introduction
  • 2 Discovery of IgM
  • 3 Structure of polymeric IgM
  • 4 Molecular requirements for forming polymeric IgM
  • 5 Tertiary and quaternary structure of the µ constant region
  • 6 Interaction of IgM with other physiological systems
  • 7 In vivo production of IgM
  • 8 Clinical significance and other points
  • 9 See also
  • 10 References
  • 11 External links

Introductionedit

Immunoglobulins, also known as antibodies, comprise a family of proteins that occur in five major forms, also termed classes or isotypes – IgM, IgD, IgG, IgE and IgA Immunoglobulins are produced by vertebrate animals as part of the normal immune response to microbial, eg, bacterial or viral, infection Binding of the immunoglobulins to the microbes can mobilize other components of the immune system to destroy or otherwise inactivate the microbes and thereby provide protection against infectious disease The molecular structures that bacteria and viruses present to the immune system and elicit immunoglobulin antibody production are collectively denoted as antigens

Although all vertebrates that have been studied – from fish to human – produce IgM, there are significant differences in the IgM of different species This article focuses on human and mouse IgM, which are both well studied and have very similar properties For the most part IgM is produced by plasma cells in the spleen and lymph nodes and secreted into serum, where it is typically at a concentration of ~15 mg/ml This article describes the structure of serum IgM, as opposed to other forms, such as the IgM membrane receptor

Immunoglobulins are composed of two types of protein chain -- the heavy chain and the light chain The heavy chains, which determine the immunoglobulin class, are of five different types, denoted by the Greek letters, µ, δ, γ, ε and α, corresponding to the classes, IgM, IgD, IgG, IgE, and IgA, respectively Light chains are of two types, denoted λ and κ Each chain is itself divided into two functional parts, the variable V domain and the constant C domain The V domains of the light and heavy chain are juxtaposed to form a structure that binds antigen; different V domains bind different antigens, ie, binding of antigen by immunoglobulin is “antigen-specific” Inasmuch as the V domains can occur in a nearly unlimited variety of amino acid sequences, immunoglobulins collectively have the potential of binding to virtually any molecular structure The immunoglobulin C domains interact with other physiological components, eg the complement system Thus, the constant domain can mobilize the complement system to act on the antigen that is bound by the variable domain

Discovery of IgMedit

The study of IgM began with the report in 1937 that horses hyperimmunized with pneumococcus polysaccharide produced antibody that was much larger than the typical rabbit γ-globulin 5, with a molecular weight of 990,000 daltons 6 In accordance with its large size, the new antibody was originally referred to as γ-macroglobulin, and then in subsequent terminology as IgM -- M for “macro” As noted above, the V domains of normal immunoglobulin are highly heterogeneous, reflecting their role in protecting against the great variety of infectious microbes, and this heterogeneity impeded detailed structural analysis of IgM Two sources of homogeneous IgM were subsequently discovered First, the high molecular weight protein produced by some myeloma patients was recognized to be tumor-produced-protein analogous to γ-macroglobulin7 Also, methods were developed in the 1960’s for inducing immunoglobulin-producing tumors plasmacytomas in mice, thus also providing a source of homogeneous immunoglobulins of various isotypes, including IgM reviewed in 8 More recently, expression of engineered immunoglobulin genes in tissue culture can be used to produce IgM with specific alternations and thus to identify the molecular requirements for features of interest

Structure of polymeric IgMedit

As noted above, immunoglobulins include light chains and heavy chains The light chain λ or κ is a protein of ~220 amino acids, composed 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 ~576 amino acids, and includes a variable domain VH ~110 amino acids, four distinct constant region domains Cµ1, Cµ2, Cµ3, Cµ4, each ~110 amino acids and a “tailpiece” of ~20 amino acids The µ heavy chain bears oligosaccharides at five asparagine residues The oligosaccharides on mouse and human IgM have been partially characterized by a variety of techniques, including NMR, lectin binding, various chromatographic systems and enzymatic sensitivity reviewed in9 The structure of the oligosaccharides at each site varies in detail, and the predominant oligosaccharides – biantennary, triantennary, high mannose --differ among the sites

Schematic model of IgM
A The µL heterodimer, sometimes called a halfmer, with variable VH, VL and constant region Cµ1, Cµ2, Cµ3, Cµ4tp; CL domains The cysteines that mediate disulfide bonds between µ chains are shown as red arrowheads, so that a cysteine disulfide bond appears as a red double arrowhead red diamond
B The IgM “monomer” µL2 The disulfide bonds between Cµ2 domains are represented by a red double arrowhead
C, D Two models for J chain-containing IgM pentamer that have appeared in various publications at various times As in B, the disulfide bonds between Cµ2 domains and the disulfide bonds between Cµ4tp domains are represented by a red double arrowhead; the Cµ3 disulfide bonds are represented for clarity by long double-headed arrows The connectivity, ie, the inter-chain disulfide bonding of the µ chains, is denoted like electrical connectivity In C the Cµ3 disulfide bonds join µ chains in parallel with the Cµ4tp disulfide bonds, and these disulfide bonds join µ chains in series with the Cµ2 disulfide bonds In D the Cµ2 and Cµ4tp disulfide bonds join µ chains in parallel and both types join µ chains in series with the Cµ3 disulfide bonds


The multimeric structure of IgM is shown schematically in Figure 1 Figure 1a shows the “heterodimer” composed of one light chain, denoted L, and one heavy chain, denoted µ The heavy and light chains are held together both by disulfide bonds depicted as red triangles and by non-covalent interactions

Figure 1b shows two µL units linked by a disulfide bond in the Cµ2 domains; this µL2 structure is often referred to as the IgM “monomer”, as it is analogous in some ways to the structure of immunoglobulin G IgG On the basis of its sedimentation velocity and appearance in electron micrographs, it was inferred that IgM is mostly a “pentamer”, ie, a polymer composed of five “monomers” µL25, and was originally depicted by the models in Figures 1c and 1d, with disulfide bonds between the Cµ3 domains and between the tail pieces 1011 Also shown is that pentameric IgM includes a third protein, the J chain J chain J for joining was discovered as a covalently bonded component of polymeric IgA and IgM 1213 J chain is a small ~137 amino acids, acidic protein As shown, J chain joins two µ chains via disulfide bonds involving cysteines in the tailpieces14

Molecular requirements for forming polymeric IgMedit

It was initially expected that J chain would be important for forming the polymeric immunoglobulins, and indeed polymerization of IgA depends strongly but not absolutely on J chain 1516 In contrast, polymeric IgM forms efficiently in the absence of J chain1718

As noted above, the predominant form of human and mouse IgM is pentamer By way of comparison, IgM from frog Xenopus is predominantly hexamer 1920, IgM from bony fish is predominantly tetramer, and IgM from cartilaginous fish shark is predominantly pentamer2122 The predominance of pentamer in mouse and human IgM notwithstanding, it was evident that these IgM’s could also exist as hexamer2324 Subsequent studies using recombinant DNA expression systems indicated that hexamer is a major form of mouse IgM, when the IgM is produced under conditions where the incorporation of J chain is prevented, either by producing IgM in cells that lack J chain17 or by producing IgM with a µ heavy chain that lacks the cysteine in the tailpiece2526 In summary, hexameric IgM never contains J chain; pentameric IgM can be formed so as to include or not include J chain 27

An important difference between the µ and γ heavy chains is the availability of cysteines for forming disulfide bonds between heavy chains In the case of the γ heavy chain, the only inter-γ bonds are formed by cysteines in the hinge, and accordingly each γ chain binds to only one other γ chain By contrast, the Cµ2and Cµ3 domains and the tailpiece each include a cysteine that form a disulfide bond with another µ chain As noted above, the cysteines in the Cµ2 domains mediate the formation of monomeric IgM µL2 The tailpiece along with the included cysteine is necessary and sufficient for the formation of polymeric immunoglobulins That is, deleting the tailpiece from the µ heavy chain prevents the formation of polymeric IgM28 Conversely, cells expressing a γ heavy chain that has been modified to include the tailpiece produce polymeric IgG293031

The role of the cysteine in the Cµ3 domain is more subtle As noted above, figures 1c and 1d represent possible models for pentameric IgM In these models each µ chain is envisaged to bind two other µ chains However, neither model alone can fully account for the structure of polymeric IgM For example, the model in Figure 1c predicts that the disulfide bond between the Cµ2 domains is essential for making disulfide-bonded polymeric IgM The model in Figure 1d predicts that the disulfide bond between the Cµ3 domains is essential In fact disulfide bonded, polymeric, IgM can still be made if any one of the three cysteines is absent In the context of models in which each µ chain interacts with only two other µ chains, these results suggest that some molecules are like Figure 1C and some like Figure 1D However, the availability of three cysteines for inter-µ chain bonding suggests that the µ chains might each bind three other µ chains, as illustrated in Figure 2 In the same spirit, figure 2C presents a model for J chain-containing pentamer that reflects evidence that J chain joins µ chains that are not joined to other µ chains by the cysteines in the Cµ3 domains These and other models, both regular and irregular are discussed elsewhere2632

Some alternative ways of linking µ chains
A, B These figures depict two of many possible models of inter-µ chain disulfide bonding in hexameric IgM As in Figure 1, the Cµ2 disulfide bonds and the Cµ4tp disulfide bonds are represented by a red double arrowhead, and the Cµ3 disulfide bonds are represented by the long double-headed arrows In both models A and B each type of disulfide bond Cµ2-Cµ2; Cµ3-Cµ3; Cµ4tp-Cµ4tp joins µ chains in series with each of the others Methods for distinguishing these and other models are discussed in reference 28
C This representation of pentameric IgM illustrates how J chain might be bonded to µ chains that are not linked via Cµ3 disulfide bonds


Pentameric IgM is typically represented as containing a single J chain per polymer, but in actuality the measurements of J chain stoichiometry have ranged from one J molecule per polymer to three J molecules per polymer33343536 The wide range might be due to technical problems, such as incomplete radiolabeling or imprecisely quantitating an Ouchterlony line However, the variation might also be due to heterogeneity in the IgM preparations, ie, the various preparations might have differed substantially in their content of J-containing and J-deficient polymers

Tertiary and quaternary structure of the µ constant regionedit

To gain insight into the detailed three-dimensional structure of the µ chain, the individual Cµ2, Cµ3 and Cµ4tp domains were produced separately in E coli and then analyzed by a variety of methods, including sedimentation rate, X-ray crystallography, and NMR spectroscopy As in the case of other immunoglobulins, the domains of the µ heavy chain have the characteristic overlying β-sheets comprising seven strands, stabilized by the intra-domain disulfide bonds Overall, the IgM constant region has a “mushroom-like” structure, where the Cµ2-Cµ3 domains are a disk analogous to the head of the mushroom and the Cµ4tp domains protrude like a short stem37

Interaction of IgM with other physiological systemsedit

As listed here and described elsewhere, IgM interacts with several other physiological molecules

  1. IgM can bind complement component C1 and activate the classical pathway, leading to opsonization of antigens and cytolysis
  2. IgM binds to the polyimmunoglobulin receptor pIgR in a process that brings IgM to mucosal surfaces, such as the gut lumen and into breast milk This binding depends on J chain38
  3. Two other Fc receptors that bind IgM have been detected The Fc/R, like pIgR, binds polymeric IgM and IgA The Fc/R can mediate endocytosis, and its expression in the gut suggests a role in mucosal immunity FcR formerly known as Toso/Faim3 binds IgM exclusively and can mediate cellular uptake of IgM-conjugated antigen39 Inactivation of the corresponding genes in knock-out mice produces a phenotype, but the physiological functions of these receptors are still uncertain4041

In vivo production of IgMedit

In germ-line cells sperm and ova the genes that will eventually encode immunoglobulins are not in a functional form see VDJ recombination In the case of the heavy chain, three germ-line segments, denoted V, D and J are ligated together and adjoined to the DNA encoding the µ heavy chain constant region Early in ontogeny, B cells express both the µ and the δ heavy chains; co-expression of these two heavy chains, each bearing the same V domain depends on alternative splicing and alternative poly-A addition sites The expression of the other isotypes γ, ε and α is effected by another type of DNA rearrangement, a process called Immunoglobulin class switching 42

Clinical significance and other pointsedit

IgM is the first immunoglobulin expressed in the human fetus around 20 weeks43 and phylogenetically the earliest antibody to develop44

IgM antibodies appear early in the course of an infection and usually reappear, to a lesser extent, after further exposure IgM antibodies do not pass across the human placenta only isotype IgG

These two biological properties of IgM make it useful in the diagnosis of infectious diseases Demonstrating IgM antibodies in a patient's serum indicates recent infection, or in a neonate's serum indicates intrauterine infection eg congenital rubella syndrome

The development of anti-donor IgM after organ transplantation is not associated with graft rejection but it may have a protective effect45

IgM in normal serum is often found to bind to specific antigens, even in the absence of prior immunization46 For this reason IgM has sometimes been called a "natural antibody" This phenomenon is probably due to the high avidity of IgM that allow it to bind detectably even to weakly cross-reacting antigens that are naturally occurring For example, the IgM antibodies that bind to the red blood cell A and B antigens might be formed in early life as a result of exposure to A- and B-like substances that are present on bacteria or perhaps also on plant materials

IgM antibodies are mainly responsible for the clumping agglutination of red blood cells if the recipient of a blood transfusion receives blood that is not compatible with their blood type

See alsoedit

  • Immunodeficiency with hyper-immunoglobulin M
  • Immunoglobulin M deficiency

Referencesedit

  1. ^ "Immunoglobulin M" The American Heritage Dictionary of the English Language Fourth ed Houghton Mifflin Company 2004  |access-date= requires |url= help
  2. ^ Bruce Alberts; Alexander Johnson; Julian Lewis; Peter Walter; Martin Raff; Keith Roberts 2002 "Chapter 24" Molecular Biology of the Cell 4th ed Routledge ISBN 978-0-8153-3288-6 
  3. ^ Racine R, McLaughlin M, Jones DD, et al 2011 "IgM production by bone marrow plasmablasts contributes to long-term protection against intracellular bacterial infection" J Immunol 186 2: 1011–21 PMC 3208352  PMID 21148037 doi:104049/jimmunol1002836 
  4. ^ "Chapter 62" Bailey & Love's Short Practice of Surgery 25th ed p 1102 
  5. ^ Heidelberger, M and K Pedersen 1937 "The molecular weight of antibodies" J Exp Med 65 3: 393–414 
  6. ^ Kabat, E "The molecular weight of antibodies" J Exp Med, 1939 691: p 103-118 
  7. ^ Waldenström, J, "Incipient myelomatisis or "essential" hyoerglobulinemis with fibrinogenopenia -- a new syndrome" Acat Med Scandinav, 1943 142: p 216-247 CS1 maint: Multiple names: authors list link
  8. ^ Potter, M "The early history of plasma cell tumors in mice, 1954-1976" Adv Cancer Res, 2007 98: p 17-51 
  9. ^ Monica, T 1995 "Characterization of the glycosylation of a human IgM produced by a human-mouse hybridoma" Glycobiology 5 2: 175–185 
  10. ^ Beale, D and A Feinstein "Studies on the Reduction of a Human 19 s Immunoglobulin M" Biochemical Journal, 1969 112: p 187-194 
  11. ^ Milstein, CP, et al, "Interchain disulfide bridges of mouse Immunoglobulin M" Biochemical Journal, 1975 151: p 615-624 CS1 maint: Multiple names: authors list link
  12. ^ Halpern, MS and ME Koshland "Novel subunit of secretory IgA" Nature, 1970 228: p 1276-1278 
  13. ^ Mestecky, J, J Zikin, and W Butler "Immunoglobulin M an secretory immunoglobulin A: presence of common polypeptide chain different from light chains" Science, 1971 171: p 1163-1165 CS1 maint: Multiple names: authors list link
  14. ^ Frutiger, S; et al "Disulfide bond assignment in human J chain and its covalent pairing with immunoglobulin M" Biochemistry, 1992 31: p 12643-12647 CS1 maint: Explicit use of et al link
  15. ^ Johansen, FE, R Braathen, and P Brandtzaeg "Role of J chain in secretory immunoglobulin formation" Scand J Immunol, 2000 523: p 240-8 CS1 maint: Multiple names: authors list link
  16. ^ Sørensen, V; et al "Structural requirements for incorporation of J chain into human IgM and IgA" Internat Immunol, 2000 121: p 19-27 CS1 maint: Explicit use of et al link
  17. ^ a b Cattaneo, A and MS Neuberger "Polymeric immunoglobulin M is secreted by transfectants of non-lymphoid cells in the absence of immunoglobulin J chain" The EMBO Journal, 1987 69: p 2753-2758 
  18. ^ Fazel, S, EJ Wiersma, and MJ Shulman "Interplay of J chain and disulfide bonding in assembly of polymeric IgM" International Immunology, 1997 9: p 1149-1158 CS1 maint: Multiple names: authors list link
  19. ^ Parkhouse, R, B Askonas, and R Dourmashkin "Electron microscopic studies of mouse immunoglobulin M; structure and reconstitution following reduction" Immunology, 1970 184: p 575-584 CS1 maint: Multiple names: authors list link
  20. ^ Schwager, J and I Hadji-Azimi "Mitogen-induced B-cell differentiation in Xenopus laevis" Differentiation, 1984 273: p 182-188 
  21. ^ Fillatreau, S; et al "The astonishing diversity of Ig classes and B cell repertoires in teleost fish" Frontiers in Immunology, 2013 4: p 1-14 CS1 maint: Explicit use of et al link
  22. ^ Getahun, A; et al "Influence of the mu-chain C-terminal sequence on polymerization of immunoglobulin M" Immunology, 1999 97: p 408-413 CS1 maint: Explicit use of et al link
  23. ^ Dolder, F "Occurrence, Isolation and Interchain Bridges of Natural 7-S Immunoglobulin M in Human Serum" Biochimica Et Biophysica Acta, 1971 236: p 675-685 
  24. ^ Eskeland, T and TB Christensen "IgM molecules with and without J chain in serum and after purification, studied by ultracentrifugation, electrophoresis, and electronmicrosopy" Scand J Immunol,, 1975 4: p 217-228 
  25. ^ Davis, AC, KH Roux, and MJ Shulman "On the structure of polymeric IgM" European Journal of Immunology, 1988 18: p 1001-1008 CS1 maint: Multiple names: authors list link
  26. ^ a b Davis, AC; et al "Intermolecular disulfide bonding in IgM: effects of replacing cysteine residues in the µ heavy chain" The EMBO Journal, 1989 89: p 2519-2526 CS1 maint: Explicit use of et al link
  27. ^ Collins, C, FW Tsui, and MJ Shulman "Differential activation of human and guinea pig complement by pentameric and hexameric IgM" Eur J Immunol, 2002 32: p 1802-1810 CS1 maint: Multiple names: authors list link
  28. ^ Davis, AC; et al "Mutations of the mouse m H chain which prevent polymer assembly" Journal of Immunology, 1989 434: p 1352-1357 CS1 maint: Explicit use of et al link
  29. ^ Smith, RIF, MJ Coloma, and SL Morrison "Addition of a m-tailpiece to IgG results in polymeric antibodies with enhanced effector functions including complement-mediated cytolysis by IgG4" Journal of Immunology, 1995 154: p 2226-2236 CS1 maint: Multiple names: authors list link
  30. ^ Sørensen, V; et al "Effect of the IgM and IgA secretory tailpieces on polymerization and secretion of IgM and IgG" Journal of Immunology, 1996 156: p 2858-2865 CS1 maint: Explicit use of et al link
  31. ^ Smith, R and S Morrison "Recombinant polymeric IgG: An approach to engineering more potent antibodies" Nature Biotechnology, 1994 12: p 683-688 
  32. ^ Wiersma, EJ and MJ Shulman "Assembly of IgM: role of disulfide bonding and noncovalent interactions" J Immunol, 1995 154: p 5265-5272 
  33. ^ Chapuis, RM and ME Koshland "Mechanism of IgM polymerization" ProcNatAcadSciUSA, 1974 713: p 657-661 
  34. ^ Mihaesco, C, E Mihaesco, and H Metzger "Variable J-chain content in human IgM" FEBS letters, 1973 372: p 303-306 CS1 maint: Multiple names: authors list link
  35. ^ Brandtzaeg, P "Complex formation between secretory component and human immunoglobulin related to their content of J chain" Scand J Immunol,, 1976 5: p 411-419 
  36. ^ Grubb, AO "Quantitation of J chain in human biological fluids by a simple immunochemical procedure" Acta Med Scand, 1978 204: p 453-465 
  37. ^ Müller, R; et al "High-resolutiion structures of the IgM Fc domainsreveal principles of its hexamer formation" Proc Natl Acad Sci U S A, 2013 11025: p 10183-10188 CS1 maint: Explicit use of et al link
  38. ^ Johansen, F E, Braathen, R & Brandtzaeg, P "Role of J chain in secretory immunoglobulin formation" Scand J Immunol 2000 52, 240-8 CS1 maint: Multiple names: authors list link
  39. ^ Shima, H; et al "Identification of TOSO/FAIM3 as an Fc receptor for IgM" Int Immunol, 2010 223: p 149-56 CS1 maint: Explicit use of et al link
  40. ^ Ouchida, R; et al "Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses" Proc Natl Acad Sci U S A, 2012 10940: p E2699-706 CS1 maint: Explicit use of et al link
  41. ^ Heidelberger, M and K Pedersen, The molecular weight of antibodies J Exp Med, 1937 653: p 393-414 2 Kabat, E, The molecular weight of antibodies J Exp Med, 1939 691: p 103-118 3 Waldenström, J, Incipient myelomatisis or "essential" hyoerglobulinemis with fibrinogenopenia -- a new syndrome Acat Med Scandinav, 1943 142: p 216-247 4 Potter, M, The early history of plasma cell tumors in mice, 1954-1976 Adv Cancer Res, 2007 98: p 17-51 5 Monica, T, et al, Characterization of the glycosylation of a human IgM produced by a human-mouse hybridoma Glycobiology, 1995 52: p 175-185 6 Beale, D and A Feinstein, Studies on the Reduction of a Human 19 s Immunoglobulin M Biochemical Journal, 1969 112: p 187-194 7 Milstein, CP, et al, Interchain disulfide bridges of mouse Immunoglobulin M Biochemical Journal, 1975 151: p 615-624 8 Halpern, MS and ME Koshland, Novel subunit of secretory IgA Nature, 1970 228: p 1276-1278 9 Mestecky, J, J Zikin, and W Butler, Immunoglobulin M an secretory immunoglobulin A: presence of common polypeptide chain different from light chains Science, 1971 171: p 1163-1165 10 Frutiger, S, et al, Disulfide bond assignment in human J chain and its covalent pairing with immunoglobulin M Biochemistry, 1992 31: p 12643-12647 11 Sørensen, V, et al, Structural requirements for incorporation of J chain into human IgM and IgA Internat Immunol, 2000 121: p 19-27 12 Johansen, FE, R Braathen, and P Brandtzaeg, Role of J chain in secretory immunoglobulin formation Scand J Immunol, 2000 523: p 240-8 13 Cattaneo, A and MS Neuberger, Polymeric immunoglobulin M is secreted by transfectants of non-lymphoid cells in the absence of immunoglobulin J chain The EMBO Journal, 1987 69: p 2753-2758 14 Fazel, S, EJ Wiersma, and MJ Shulman, Interplay of J chain and disulfide bonding in assembly of polymeric IgM International Immunology, 1997 9: p 1149-1158 15 Parkhouse, R, B Askonas, and R Dourmashkin, Electron microscopic studies of mouse immunoglobulin M; structure and reconstitution following reduction Immunology, 1970 184: p 575-584 16 Schwager, J and I Hadji-Azimi, Mitogen-induced B-cell differentiation in Xenopus laevis Differentiation, 1984 273: p 182-188 17 Fillatreau, S, et al, The astonishing diversity of Ig classes and B cell repertoires in teleost fish Frontiers in Immunology, 2013 4: p 1-14 18 Getahun, A, et al, Influence of the mu-chain C-terminal sequence on polymerization of immunoglobulin M Immunology, 1999 97: p 408-413 19 Dolder, F, Occurrence, Isolation and Interchain Bridges of Natural 7-S Immunoglobulin M in Human Serum Biochimica Et Biophysica Acta, 1971 236: p 675-685 20 Eskeland, T and TB Christensen, IgM molecules with and without J chain in serum and after purification, studied by ultracentrifugation, electrophoresis, and electronmicrosopy Scand J Immunol,, 1975 4: p 217-228 21 Davis, AC, KH Roux, and MJ Shulman, On the structure of polymeric IgM European Journal of Immunology, 1988 18: p 1001-1008 22 Davis, AC, et al, Intermolecular disulfide bonding in IgM: effects of replacing cysteine residues in the µ heavy chain The EMBO Journal, 1989 89: p 2519-2526 23 Collins, C, FW Tsui, and MJ Shulman, Differential activation of human and guinea pig complement by pentameric and hexameric IgM Eur J Immunol, 2002 32: p 1802-1810 24 Davis, AC, et al, Mutations of the mouse m H chain which prevent polymer assembly The Journal of Immunology, 1989 434: p 1352-1357 25 Smith, RIF, MJ Coloma, and SL Morrison, Addition of a m-tailpiece to IgG results in polymeric antibodies with enhanced effector functions including complement-mediated cytolysis by IgG4 Journal of Immunology, 1995 154: p 2226-2236 26 Sørensen, V, et al, Effect of the IgM and IgA secretory tailpieces on polymerization and secretion of IgM and IgG The Journal of Immunology, 1996 156: p 2858-2865 27 Smith, R and S Morrison, Recombinant polymeric IgG: An approach to engineering more potent antibodies Nature Biotechnology, 1994 12: p 683-688 28 Wiersma, EJ and MJ Shulman, Assembly of IgM: role of disulfide bonding and noncovalent interactions J Immunol, 1995 154: p 5265-5272 29 Chapuis, RM and ME Koshland, Mechanism of IgM polymerization ProcNatAcadSciUSA, 1974 713: p 657-661 30 Mihaesco, C, E Mihaesco, and H Metzger, Variable J-chain content in human IgM FEBS letters, 1973 372: p 303-306 31 Brandtzaeg, P, Complex formation between secretory component and human immunoglobulin related to their content of J chain Scand J Immunol,, 1976 5: p 411-419 32 Grubb, AO, Quantitation of J chain in human biological fluids by a simple immunochemical procedure Acta Med Scand, 1978 204: p 453-465 33 Müller, R, et al, High-resolutiion structures of the IgM Fc domainsreveal principles of its hexamer formation Proc Natl Acad Sci U S A, 2013 11025: p 10183-10188 34 Shima, H, et al, Identification of TOSO/FAIM3 as an Fc receptor for IgM Int Immunol, 2010 223: p 149-56 35 Ouchida, R, et al, Critical role of the IgM Fc receptor in IgM homeostasis, B-cell survival, and humoral immune responses Proc Natl Acad Sci U S A, 2012 10940: p E2699-706 36 Kubagawa, H; et al "The old but new IgM Fc receptor FcmuR" Curr Top Microbiol Immunol, 2014 382: p 3-28  horizontal tab character in |last1= at position 112 helpCS1 maint: Explicit use of et al linkCS1 maint: Multiple names: authors list link
  42. ^ Murphy, K; Weaver, C 2016 Janeway's Immunobiology New York, NY: Garland Science/Taylor and Francis p 195 ISBN 9780815345053 
  43. ^ van Furth R, Schuit HR, Hijmans W 1965 "The immunological development of the human fetus" J Exp Med 122 6: 1173–88 PMC 2138097  PMID 4159036 doi:101084/jem12261173 CS1 maint: Uses authors parameter link
  44. ^ Review of Medical Physiology by William Francis Ganong
  45. ^ McAlister CC, Gao ZH, McAlister VC, et al February 2004 "Protective anti-donor IgM production after crossmatch positive liver-kidney transplantation" Liver Transpl 10 2: 315–9 PMID 14762873 doi:101002/lt20062 
  46. ^ Jayasekera JP, Moseman EA, Carroll MC 2007 "Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity" J Virol 81 7: 3487–94 PMC 1866020  PMID 17202212 doi:101128/JVI02128-06 

External linksedit

  • Immunoglobulin M at the US National Library of Medicine Medical Subject Headings MeSH
  • Immunoglobulin M Deficiency Reference from Medscapecom

immunoglobulin m, immunoglobulin m (igm), immunoglobulin m blood test, immunoglobulin m deficiency, immunoglobulin m elevation, immunoglobulin m high level, immunoglobulin m qn serum, immunoglobulin m serum, immunoglobulin meaning, immunoglobulin molecule


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