immunoglobulin d


Summary: An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B LYMPHOCYTES.

Top Publications

  1. Houten S, Koster J, Romeijn G, Frenkel J, Di Rocco M, Caruso U, et al. Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. Eur J Hum Genet. 2001;9:253-9 pubmed
  2. Xu B, Wang J, Zhang M, Wang P, Wei Z, Sun Y, et al. Expressional analysis of immunoglobulin D in cattle (Bos taurus), a large domesticated ungulate. PLoS ONE. 2012;7:e44719 pubmed publisher
    For decades, it has remained unknown whether artiodactyls, such as cattle, pigs, and sheep, express immunoglobulin D (IgD), although the ? gene was identified in these species nearly 10 years ago...
  3. Ramírez Gómez F, Greene W, Rego K, Hansen J, Costa G, Kataria P, et al. Discovery and characterization of secretory IgD in rainbow trout: secretory IgD is produced through a novel splicing mechanism. J Immunol. 2012;188:1341-9 pubmed publisher
    ..Our data demonstrate that secretory IgD is more prevalent and widespread across taxa than previously thought, and thus illustrate the potential that IgD may have a conserved role in immunity...
  4. Morris C, Drake M, Apperley J, Iacobelli S, van Biezen A, Bjorkstrand B, et al. Efficacy and outcome of autologous transplantation in rare myelomas. Haematologica. 2010;95:2126-33 pubmed publisher
    ..The overall survival of patients with IgD, IgE or IgM myeloma is poor following autologous transplantation but substantially better than that reported for patients who were not transplanted. ..
  5. Chang H, Chou W, Lee S, Huang J, Hung Y. Myelomatous pleural effusion in a patient with plasmablastic myeloma: a case report. Diagn Cytopathol. 2009;37:205-7 pubmed publisher
    ..The patient had multiple risk factors for inferior prognosis of multiple myeloma, including old age, immunoglobulin D (IgD) isotype, high lactate dehydrogenase, C-reactive protein, beta2-microglogulin levels, and a high myeloma ..
  6. Duty J, Szodoray P, Zheng N, Koelsch K, Zhang Q, Swiatkowski M, et al. Functional anergy in a subpopulation of naive B cells from healthy humans that express autoreactive immunoglobulin receptors. J Exp Med. 2009;206:139-51 pubmed publisher
    ..This is the first identification of a distinct mature human B cell subset that is naturally autoreactive and controlled by the tolerizing mechanism of functional anergy. ..
  7. Jendholm J, Samuelsson M, Cardell L, Forsgren A, Riesbeck K. Moraxella catarrhalis-dependent tonsillar B cell activation does not lead to apoptosis but to vigorous proliferation resulting in nonspecific IgM production. J Leukoc Biol. 2008;83:1370-8 pubmed publisher
  8. Tan T, Christensen J, Dziegiel M, Forsgren A, Riesbeck K. Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D-binding outer membrane protein and the ubiquitous surface proteins A1 and A2. Infect Immun. 2006;74:6377-86 pubmed
    Moraxella catarrhalis immunoglobulin D-binding protein (MID) is a complex antigen with unique immunoglobulin D (IgD)-binding, adhesion, and hemagglutination properties...
  9. Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K. Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol. 2005;175:3262-7 pubmed
    ..Although diminished function itself of aged B cells surely exist, decline of the IgM memory B cell pool is expected to result in a poor humoral immunity against pneumococcal infection in elderly people. ..

More Information


  1. Nordstrom T, Forsgren A, Riesbeck K. The immunoglobulin D-binding part of the outer membrane protein MID from Moraxella catarrhalis comprises 238 amino acids and a tetrameric structure. J Biol Chem. 2002;277:34692-9 pubmed
    ..Interestingly, tetrameric MID(962-1200) attracted IgD more than 20-fold more efficiently than the monomeric form. Thus, a tetrameric structure of MID(962-1200) is crucial for optimal IgD-binding capacity. ..
  2. Hordvik I. Identification of a novel immunoglobulin delta transcript and comparative analysis of the genes encoding IgD in Atlantic salmon and Atlantic halibut. Mol Immunol. 2002;39:85-91 pubmed
    ..Thus, the duplicated gene fragments have either arisen independently in each species or are subjected to homogenisation by some means. ..
  3. Samuelsson M, Forsgren A, Riesbeck K. Purification of IgD from human serum--a novel application of recombinant M. catarrhalis IgD-binding protein (MID). J Immunol Methods. 2006;317:31-7 pubmed
    ..Our approach reduces the non-specificity commonly associated with lectin-based IgD purification regimes that rely on glycosylation of the IgD molecule. ..
  4. Sanz I, Wei C, Lee F, Anolik J. Phenotypic and functional heterogeneity of human memory B cells. Semin Immunol. 2008;20:67-82 pubmed publisher
  5. Chen K, Cerutti A. New insights into the enigma of immunoglobulin D. Immunol Rev. 2010;237:160-79 pubmed publisher
    b>Immunoglobulin D (IgD) has remained a mysterious antibody class for almost half a century...
  6. Roll P, Dorner T, Tony H. Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment. Arthritis Rheum. 2008;58:1566-75 pubmed publisher
    ..The effects on B cell homeostasis after repeated treatments and the relationship of certain B cell subsets to clinical response or relapse are currently not known...
  7. Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet. 2006;367:740-8 pubmed
    ..Whether this approach would also allow improved protection against lower respiratory tract infections warrants further investigation. ..
  8. Stojanov S, Lohse P, Lohse P, Hoffmann F, Renner E, Zellerer S, et al. Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the p. Arthritis Rheum. 2004;50:1951-8 pubmed
  9. Saha N, Suetake H, Kikuchi K, Suzuki Y. Fugu immunoglobulin D: a highly unusual gene with unprecedented duplications in its constant region. Immunogenetics. 2004;56:438-47 pubmed publisher
    ..The expression pattern is similar to that of IgM, corroborating the hypothesis that IgD plays an important role in the humoral immune system of this species...
  10. Nordstrom T, Jendholm J, Samuelsson M, Forsgren A, Riesbeck K. The IgD-binding domain of the Moraxella IgD-binding protein MID (MID962-1200) activates human B cells in the presence of T cell cytokines. J Leukoc Biol. 2006;79:319-29 pubmed
    Moraxella catarrhalis immunoglobulin D (IgD)-binding protein (MID) is an outer membrane protein with specific affinity for soluble and cell-bound human IgD. Here, we demonstrate that mutated M...
  11. Conacher M, Callard R, McAulay K, Chapel H, Webster D, Kumararatne D, et al. Epstein-Barr virus can establish infection in the absence of a classical memory B-cell population. J Virol. 2005;79:11128-34 pubmed
    ..Our results demonstrate that short-term EBV persistence can occur in the absence of a germinal center reaction and a classical memory B-cell population. ..
  12. Hansen J, Landis E, Phillips R. Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish. Proc Natl Acad Sci U S A. 2005;102:6919-24 pubmed
    ..All three isotypes are primarily expressed in the spleen and pronephros (bone marrow equivalent), and ontogenically, expression of IgT is present 4 d before hatching in developing embryos. ..
  13. Koelsch K, Zheng N, Zhang Q, Duty A, Helms C, Mathias M, et al. Mature B cells class switched to IgD are autoreactive in healthy individuals. J Clin Invest. 2007;117:1558-65 pubmed
    ..Determination of the mechanism by which the majority of C delta-CS B cells are autoreactive may be important in understanding peripheral tolerance mechanisms and may provide insight into the enigmatic function of the IgD antibody. ..
  14. Rogers K, Richardson J, Scinicariello F, Attanasio R. Molecular characterization of immunoglobulin D in mammals: immunoglobulin heavy constant delta genes in dogs, chimpanzees and four old world monkey species. Immunology. 2006;118:88-100 pubmed
    Antibodies are adaptor molecules that neutralize pathogens and link humoral and cellular defence mechanisms. Immunoglobulin D (IgD), one of the five antibody classes present in mammals, is expressed as an antigen receptor on naïve B ..
  15. Forsgren A, Brant M, Möllenkvist A, Muyombwe A, Janson H, Woin N, et al. Isolation and characterization of a novel IgD-binding protein from Moraxella catarrhalis. J Immunol. 2001;167:2112-20 pubmed
    ..MID also bound to the surface-expressed B cell receptor IgD, but not to other membrane molecules on human PBLs. This novel Ig-binding reagent promises to be of theoretical and practical interest in immunological research. ..
  16. Cariappa A, Mazo I, Chase C, Shi H, Liu H, Li Q, et al. Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes. Immunity. 2005;23:397-407 pubmed
    ..The bone marrow represents a unique type of secondary lymphoid organ in which mature B cells are strategically positioned in the path of circulating microbes. ..
  17. Gjörloff Wingren A, Hadzic R, Forsgren A, Riesbeck K. The novel IgD binding protein from Moraxella catarrhalis induces human B lymphocyte activation and Ig secretion in the presence of Th2 cytokines. J Immunol. 2002;168:5582-8 pubmed
    ..Taken together, MID has properties that make it an important tool to study IgD-targeted activation of B cells. ..
  18. Chevallier B, Vesikari T, Brzostek J, Knuf M, Bermal N, Aristegui J, et al. Safety and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with routine childhood vaccines. Pediatr Infect Dis J. 2009;28:S109-18 pubmed publisher
  19. Wysocki J, Tejedor J, Grunert D, Konior R, Garcia Sicilia J, Knuf M, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with different neisseria meningitidis serogroup C conjugate vaccines. Pediatr Infect Dis J. 2009;28:S77-88 pubmed publisher
    ..PHiD-CV was immunogenic when coadministered with other routine pediatric vaccines including MenC conjugate vaccines. ..
  20. Shi Y, Agematsu K, Ochs H, Sugane K. Functional analysis of human memory B-cell subpopulations: IgD+CD27+ B cells are crucial in secondary immune response by producing high affinity IgM. Clin Immunol. 2003;108:128-37 pubmed
  21. Seifert M, Kuppers R. Molecular footprints of a germinal center derivation of human IgM+(IgD+)CD27+ B cells and the dynamics of memory B cell generation. J Exp Med. 2009;206:2659-69 pubmed publisher
    ..This provides novel insights into the dynamics of GC reactions and the generation of a memory B cell repertoire. ..
  22. Wu Y, Kipling D, Leong H, Martin V, Ademokun A, Dunn Walters D. High-throughput immunoglobulin repertoire analysis distinguishes between human IgM memory and switched memory B-cell populations. Blood. 2010;116:1070-8 pubmed publisher
    ..Thus we conclude that a large proportion of IgM memory cells develop in response to different stimuli than for class-switched memory cell development...
  23. Preud homme J, Petit I, Barra A, Morel F, Lecron J, Lelievre E. Structural and functional properties of membrane and secreted IgD. Mol Immunol. 2000;37:871-87 pubmed
  24. Bodar E, van der Hilst J, van Heerde W, Van der Meer J, Drenth J, Simon A. Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome. Blood. 2007;109:2416-8 pubmed
  25. Chen K, Xu W, Wilson M, He B, Miller N, Bengten E, et al. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat Immunol. 2009;10:889-98 pubmed publisher
    b>Immunoglobulin D (IgD) is an enigmatic antibody isotype that mature B cells express together with IgM through alternative RNA splicing...
  26. Scheeren F, Nagasawa M, Weijer K, Cupedo T, Kirberg J, Legrand N, et al. T cell-independent development and induction of somatic hypermutation in human IgM+ IgD+ CD27+ B cells. J Exp Med. 2008;205:2033-42 pubmed publisher
    ..Using Rag2(-/-)gamma(C)(-/-) mice on a Nude background, we demonstrated that development and induction of SHMs of human IgM(+)IgD(+)CD27(+) B cells can occur in a T cell-independent manner. ..
  27. Reece D, Vesole D, Shrestha S, Zhang M, Perez W, Dispenzieri A, et al. Outcome of patients with IgD and IgM multiple myeloma undergoing autologous hematopoietic stem cell transplantation: a retrospective CIBMTR study. Clin Lymphoma Myeloma Leuk. 2010;10:458-63 pubmed publisher
    b>Immunoglobulin D (IgD) and IgM multiple myeloma represent uncommon immunoglobulin isotypes, accounting for 2% and 0.5% of cases, respectively...
  28. Cuisset L, Drenth J, Simon A, Vincent M, van der Velde Visser S, van der Meer J, et al. Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet. 2001;9:260-6 pubmed
    ..Three patients are also described to illustrate the genotypic and phenotypic overlap with mevalonic aciduria. ..
  29. Bengten E, Quiniou S, Stuge T, Katagiri T, Miller N, Clem L, et al. The IgH locus of the channel catfish, Ictalurus punctatus, contains multiple constant region gene sequences: different genes encode heavy chains of membrane and secreted IgD. J Immunol. 2002;169:2488-97 pubmed
    ..The third delta (IGHD2) is associated with a pseudo C micro (IGHM2P); its presence is inferred by Southern blot analyses...
  30. Houten S, Frenkel J, Rijkers G, Wanders R, Kuis W, Waterham H. Temperature dependence of mutant mevalonate kinase activity as a pathogenic factor in hyper-IgD and periodic fever syndrome. Hum Mol Genet. 2002;11:3115-24 pubmed
    ..Our results suggest that minor elevations in temperature can set off a chain of events with MK becoming progressively rate-limiting, leading to a temporary deficiency of isoprenoid end-products, which induces inflammation and fever. ..
  31. Sinclair D. IgD myeloma: clinical, biological and laboratory features. Clin Lab. 2002;48:617-22 pubmed
    ..However, the management of any associated renal failure will always remain a challenge, I suspect. The progress being made in the treatment of myeloma as a whole, is bound to have a positive impact on the treatment of IgD myeloma. ..
  32. Johansen F, Baekkevold E, Carlsen H, Farstad I, Soler D, Brandtzaeg P. Regional induction of adhesion molecules and chemokine receptors explains disparate homing of human B cells to systemic and mucosal effector sites: dispersion from tonsils. Blood. 2005;106:593-600 pubmed
    ..However, immunization of nasopharynx-associated lymphoid tissue clearly appears preferable to target respiratory pathogens and may to some extent also protect against infections of the female genital tract. ..
  33. Willer D, Speck S. Long-term latent murine Gammaherpesvirus 68 infection is preferentially found within the surface immunoglobulin D-negative subset of splenic B cells in vivo. J Virol. 2003;77:8310-21 pubmed
    ..Furthermore, at late times postinfection latent gammaHV68 is largely confined to the surface immunoglobulin D-negative subset of B cells.
  34. Hayashi T, Yamaguchi I, Saitoh H, Takagi M, Nonaka Y, Nomura T. Thalidomide treatment for immunoglobulin D multiple myeloma in a patient on chronic hemodialysis. Intern Med. 2003;42:605-8 pubmed
    ..Thalidomide represents a valid therapeutic option for some myeloma patients receiving hemodialysis. ..
  35. Simon A, Kremer H, Wevers R, Scheffer H, De Jong J, van der Meer J, et al. Mevalonate kinase deficiency: Evidence for a phenotypic continuum. Neurology. 2004;62:994-7 pubmed
    ..psychomotor retardation, cerebellar ataxia, recurrent fever attacks, and death in early childhood, and hyper-immunoglobulin D (hyper-IgD) syndrome, with recurrent fever attacks without neurologic symptoms, are caused by a functional ..
  36. Jendholm J, Morgelin M, Perez Vidakovics M, Carlsson M, Leffler H, Cardell L, et al. Superantigen- and TLR-dependent activation of tonsillar B cells after receptor-mediated endocytosis. J Immunol. 2009;182:4713-20 pubmed publisher
    ..In conclusion, our findings suggest an important role of TLRs in the adaptive immune response and reveal novel insights into the T cell-independent B cell activation induced by bacteria. ..
  37. Wei C, Anolik J, Cappione A, Zheng B, Pugh Bernard A, Brooks J, et al. A new population of cells lacking expression of CD27 represents a notable component of the B cell memory compartment in systemic lupus erythematosus. J Immunol. 2007;178:6624-33 pubmed
    ..These findings enhance our understanding of the B cell diversification pathways and provide mechanistic insight into the immunopathogenesis of SLE...
  38. Bodar E, van der Hilst J, Drenth J, van der Meer J, Simon A. Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. Neth J Med. 2005;63:260-4 pubmed
    ..In this patient, the IL-1ra analogue anakinra was more successful in aborting the inflammatory attack than etanercept. We propose that this vaccination model will allow evaluation of treatment-on-demand in a controlled setting. ..
  39. Bemelmans R, van Toorn D, van Leeuwen L, Schaar C. Long-term complete remission in IgD-myeloma. Eur J Haematol. 2006;76:339-41 pubmed
    ..This is remarkable, considering that several adverse prognostic factors were present. In addition a concise review on IgD-MM is given. ..
  40. Weller S, Mamani Matsuda M, Picard C, Cordier C, Lecoeuche D, Gauthier F, et al. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+ IgD+ CD27+ B cell repertoire in infants. J Exp Med. 2008;205:1331-42 pubmed publisher
    ..These data provide evidence for the developmental diversification of IgM(+)IgD(+)CD27(+) B cells, at least in very young children, outside of T cell-dependent and -independent immune responses...
  41. Oretti C, Barbi E, Marchetti F, Lepore L, Ventura A, D Osualdo A, et al. Diagnostic challenge of hyper-IgD syndrome in four children with inflammatory gastrointestinal complaints. Scand J Gastroenterol. 2006;41:430-6 pubmed
    ..Gastrointestinal complaints associated with recurrent fever and mesenteric adenopathy warrant genetic investigation for HIDS, in order to avoid unnecessary invasive investigations and treatment. ..
  42. Vilen B, Burke K, Sleater M, Cambier J. Transmodulation of BCR signaling by transduction-incompetent antigen receptors: implications for impaired signaling in anergic B cells. J Immunol. 2002;168:4344-51 pubmed
    ..Thus, BCR destabilization may underlie the Ag unresponsiveness of anergic B cells. ..
  43. Frenkel J, Willemsen M, Weemaes C, Dorland L, Mayatepek E. Increased urinary leukotriene E(4) during febrile attacks in the hyperimmunoglobulinaemia D and periodic fever syndrome. Arch Dis Child. 2001;85:158-9 pubmed
    ..As no effective treatment is yet available, leukotriene receptor antagonists might offer a new therapeutic approach for patients with the hyperimmunoglobulinaemia D and periodic fever syndrome. ..
  44. Vesikari T, Wysocki J, Chevallier B, Karvonen A, Czajka H, Arsène J, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) compared to the licensed 7vCRM vaccine. Pediatr Infect Dis J. 2009;28:S66-76 pubmed publisher
    ..Effective priming is further indicated by robust booster responses. ..
  45. Bermal N, Szenborn L, Chrobot A, Alberto E, Lommel P, Gatchalian S, et al. The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity. Pediatr Infect Dis J. 2009;28:S89-96 pubmed publisher
    ..PHiD-CV was immunogenic against each of the 10 pneumococcal vaccine serotypes when coadministered with DTPw-HBV/Hib and poliovirus vaccines. ..
  46. Jacobi A, Reiter K, Mackay M, Aranow C, Hiepe F, Radbruch A, et al. Activated memory B cell subsets correlate with disease activity in systemic lupus erythematosus: delineation by expression of CD27, IgD, and CD95. Arthritis Rheum. 2008;58:1762-73 pubmed publisher
    ..Focusing on CD27- B cells, this study aimed to identify abnormalities in peripheral B cell subsets in patients with SLE...
  47. Möllenkvist A, Nordstrom T, Hallden C, Christensen J, Forsgren A, Riesbeck K. The Moraxella catarrhalis immunoglobulin D-binding protein MID has conserved sequences and is regulated by a mechanism corresponding to phase variation. J Bacteriol. 2003;185:2285-95 pubmed
    The prevalence of the Moraxella catarrhalis immunoglobulin D (IgD)-binding outer membrane protein MID and its gene was determined in 91 clinical isolates and in 7 culture collection strains...
  48. Edholm E, Bengten E, Stafford J, Sahoo M, Taylor E, Miller N, et al. Identification of two IgD+ B cell populations in channel catfish, Ictalurus punctatus. J Immunol. 2010;185:4082-94 pubmed publisher
    ..Together, these findings imply that catfish IgM(-)/IgD(+) B cells likely expand in response to certain pathogens and that the catfish IgD Fc-region, as has been suggested for human IgD, may function as a pattern recognition molecule. ..
  49. Sun Y, Wei Z, Hammarstrom L, Zhao Y. The immunoglobulin ? gene in jawed vertebrates: a comparative overview. Dev Comp Immunol. 2011;35:975-81 pubmed publisher
    b>Immunoglobulin D (IgD) was recently suggested to be an ancient Ig class, as old as IgM, arising approximately 500 million years ago. Its encoding gene has now been identified in nearly all classes of jawed vertebrates (except birds)...
  50. Smith A, de Wolff J, Molyneux K, Feehally J, Barratt J. O-glycosylation of serum IgD in IgA nephropathy. J Am Soc Nephrol. 2006;17:1192-9 pubmed
    ..These observations show that abnormal IgA1 O-glycosylation in IgAN is not due to an inherent defect in glycosylation mechanisms but arises only at a later stage in B cell development and may be secondary to aberrant immunoregulation. ..
  51. Frenkel J, Houten S, Waterham H, Wanders R, Rijkers G, Duran M, et al. Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D. Rheumatology (Oxford). 2001;40:579-84 pubmed
    ..Periodic fever and elevated IgD can result from other, still unknown, causes. Hence, testing for MK deficiency is necessary in patients with unexplained periodic fever. ..
  52. Medlej Hashim M, Petit I, Adib S, Chouery E, Salem N, Delague V, et al. Familial Mediterranean Fever: association of elevated IgD plasma levels with specific MEFV mutations. Eur J Hum Genet. 2001;9:849-54 pubmed
    ..Elevated IgD plasma levels are also correlated with the severity of FMF manifestations, and especially with arthritis. ..
  53. Gala F, Morrison S. The role of constant region carbohydrate in the assembly and secretion of human IgD and IgA1. J Biol Chem. 2002;277:29005-11 pubmed
    ..Thus, one N-linked glycan plays a structural role in IgD and is required for proper assembly and secretion, but the O-linked carbohydrates in the hinge of IgD and IgA1 are not required for folding and export. ..