Analyze Diet
Immunogenetics2014; 66(11); 635-649; doi: 10.1007/s00251-014-0799-9

Hematopoiesis in the equine fetal liver suggests immune preparedness.

Abstract: We investigated how the equine fetus prepares its pre-immune humoral repertoire for an imminent exposure to pathogens in the neonatal period, particularly how the primary hematopoietic organs are equipped to support B cell hematopoiesis and immunoglobulin (Ig) diversity. We demonstrated that the liver and the bone marrow at approximately 100 days of gestation (DG) are active sites of hematopoiesis based on the expression of signature messenger RNA (mRNA) (c-KIT, CD34, IL7R, CXCL12, IRF8, PU.1, PAX5, NOTCH1, GATA1, CEBPA) and protein markers (CD34, CD19, IgM, CD3, CD4, CD5, CD8, CD11b, CD172A) of hematopoietic development and leukocyte differentiation molecules, respectively. To verify Ig diversity achieved during the production of B cells, V(D)J segments were sequenced in primary lymphoid organs of the equine fetus and adult horse, revealing that similar heavy chain VDJ segments and CDR3 lengths were most frequently used independent of life stage. In contrast, different lambda light chain segments were predominant in equine fetal compared to adult stage, and surprisingly, the fetus had less restricted use of variable gene segments to construct the lambda chain. Fetal Igs also contained elements of sequence diversity, albeit to a smaller degree than that of the adult horse. Our data suggest that the B cells produced in the liver and bone marrow of the equine fetus generate a wide repertoire of pre-immune Igs for protection, and the more diverse use of different lambda variable gene segments in fetal life may provide the neonate an opportunity to respond to a wider range of antigens at birth.
Publication Date: 2014-09-02 PubMed ID: 25179685PubMed Central: PMC4198492DOI: 10.1007/s00251-014-0799-9Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • N.I.H.
  • Extramural

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study focuses on how the equine fetus readies its immune system, particularly its B cells and immunoglobulins, for exposure to pathogens after birth. The researchers found the liver and bone marrow of the fetus to be active sites for the development of these immune components, and noted that the range of antibodies produced is wide and varied, increasing the potential for an effective response to a variety of antigens once the foal is born.

Hematopoiesis in Equine Fetal Liver and Bone Marrow

The study knows that hematopoiesis (the production of blood cells) is actively taking place in the liver and bone marrow of the equine fetus. This was deduced from the detection of:

  • Specific mRNA (c-KIT, CD34, IL7R, CXCL12, IRF8, PU.1, PAX5, NOTCH1, GATA1, CEBPA), which are key markers of hematopoietic development and leukocyte differentiation. These markers help decode the development and uniqueness of blood and immune cells.
  • Protein markers (CD34, CD19, IgM, CD3, CD4, CD5, CD8, CD11b, CD172A), which also help identify different stages and types of hematopoietic and leukocyte development.

B Cell Production and Immunoglobulin Diversity

The researchers sought to determine the diversity of immunoglobulin (Ig) produced by the B cells in the fetus. This was done by sequencing V(D)J segments – sections of the DNA in B cells responsible for producing a wide variety of antibodies. The study found that:

  • Both the equine fetus and adult horse utilized similar heavy chain VDJ segments and CDR3 lengths most frequently.
  • Different lambda light chain segments (another part of the antibody) were more commonly used in the fetal stage than in the adult stage.
  • Interestingly, the fetus used a more varied selection of variable gene segments to construct the lambda chain, suggesting a more diversified response to antigens.
  • Moreover, whilst the sequence diversity of fetal Igs was found to be lesser than that of the adult horse, the study implies that the fetus’s wider use of lambda variable gene segments and diversity in B cell production equips the newborn with an ability to react to a broader range of antigens right after birth.

Cite This Article

APA
Battista JM, Tallmadge RL, Stokol T, Felippe MJ. (2014). Hematopoiesis in the equine fetal liver suggests immune preparedness. Immunogenetics, 66(11), 635-649. https://doi.org/10.1007/s00251-014-0799-9

Publication

ISSN: 1432-1211
NlmUniqueID: 0420404
Country: United States
Language: English
Volume: 66
Issue: 11
Pages: 635-649

Researcher Affiliations

Battista, J M
  • Equine Immunology Lab, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA, jmb279@cornell.edu.
Tallmadge, R L
    Stokol, T
      Felippe, M J B

        MeSH Terms

        • Animals
        • Antibody Diversity / genetics
        • Antibody Diversity / immunology
        • B-Lymphocytes / immunology
        • Bone Marrow / immunology
        • Fetus / immunology
        • Hematopoiesis / genetics
        • Hematopoiesis / immunology
        • Horses / genetics
        • Horses / immunology
        • Immunoglobulin Heavy Chains / genetics
        • Immunoglobulin Heavy Chains / immunology
        • Immunoglobulin Variable Region / genetics
        • Immunoglobulin Variable Region / immunology
        • Immunoglobulin lambda-Chains / genetics
        • Immunoglobulin lambda-Chains / immunology
        • Leukocytes / immunology
        • Liver / immunology
        • RNA, Messenger / genetics
        • RNA, Messenger / immunology

        Grant Funding

        • DP2 OD007216 / NIH HHS
        • 1 DP2 OD007216 / NIH HHS

        References

        This article includes 77 references
        1. Almagro JC, Martinez L, Smith SL, Alagon A, Estevez J, Paniagua J. Analysis of the horse V(H) repertoire and comparison with the human IGHV germline genes, and sheep, cattle and pig V(H) sequences.. Mol Immunol 2006 Apr;43(11):1836-45.
          pubmed: 16337682doi: 10.1016/j.molimm.2005.10.017google scholar: lookup
        2. Bangs LA, Sanz IE, Teale JM. Comparison of D, JH, and junctional diversity in the fetal, adult, and aged B cell repertoires.. J Immunol 1991 Mar 15;146(6):1996-2004.
          pubmed: 1672338
        3. Barrios Y, Jirholt P, Ohlin M. Length of the antibody heavy chain complementarity determining region 3 as a specificity-determining factor.. J Mol Recognit 2004 Jul-Aug;17(4):332-8.
          pubmed: 15227640doi: 10.1002/jmr.679google scholar: lookup
        4. Becker RS, Knight KL. Somatic diversification of immunoglobulin heavy chain VDJ genes: evidence for somatic gene conversion in rabbits.. Cell 1990 Nov 30;63(5):987-97.
          pubmed: 2124176doi: 10.1016/0092-8674(90)90502-6google scholar: lookup
        5. Berland R, Wortis HH. Origins and functions of B-1 cells with notes on the role of CD5.. Annu Rev Immunol 2002;20:253-300.
        6. Butler JE, Wertz N, Sun X. Antibody repertoire development in fetal and neonatal piglets. XIV. Highly restricted IGKV gene usage parallels the pattern seen with IGLV and IGHV.. Mol Immunol 2013 Oct;55(3-4):329-36.
          pubmed: 23618164doi: 10.1016/j.molimm.2013.03.011google scholar: lookup
        7. Butler JE, Sun X, Wertz N, Lager KM, Chaloner K, Urban J Jr, Francis DL, Nara PL, Tobin GJ. Antibody repertoire development in fetal and neonatal piglets XXI. Usage of most VH genes remains constant during fetal and postnatal development.. Mol Immunol 2011 Dec;49(3):483-94.
          pubmed: 22018637doi: 10.1016/j.molimm.2011.09.018google scholar: lookup
        8. Butler JE, Sun J, Wertz N, Sinkora M. Antibody repertoire development in swine.. Dev Comp Immunol 2006;30(1-2):199-221.
          pubmed: 16168480doi: 10.1016/j.dci.2005.06.025google scholar: lookup
        9. Butler JE, Weber P, Sinkora M, Sun J, Ford SJ, Christenson RK. Antibody repertoire development in fetal and neonatal piglets. II. Characterization of heavy chain complementarity-determining region 3 diversity in the developing fetus.. J Immunol 2000 Dec 15;165(12):6999-7010.
          pubmed: 11120827doi: 10.4049/jimmunol.165.12.6999google scholar: lookup
        10. Cobaleda C, Schebesta A, Delogu A, Busslinger M. Pax5: the guardian of B cell identity and function.. Nat Immunol 2007 May;8(5):463-70.
          pubmed: 17440452doi: 10.1038/ni1454google scholar: lookup
        11. Das S, Nozawa M, Klein J, Nei M. Evolutionary dynamics of the immunoglobulin heavy chain variable region genes in vertebrates.. Immunogenetics 2008 Jan;60(1):47-55.
          pmc: PMC2386433pubmed: 18196235doi: 10.1007/s00251-007-0270-2google scholar: lookup
        12. Delassus S, Darche S, Kourilsky P, Cumano A. Ontogeny of the heavy chain immunoglobulin repertoire in fetal liver and bone marrow.. J Immunol 1998 Apr 1;160(7):3274-80.
          pubmed: 9531284
        13. Desiderio SV, Yancopoulos GD, Paskind M, Thomas E, Boss MA, Landau N, Alt FW, Baltimore D. Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells.. Nature 1984 Oct 25-31;311(5988):752-5.
          pubmed: 6092963doi: 10.1038/311752a0google scholar: lookup
        14. Di Noia JM, Neuberger MS. Molecular mechanisms of antibody somatic hypermutation.. Annu Rev Biochem 2007;76:1-22.
        15. Douglas RH, Ginther OJ. Effects of repeated daily injections of prostaglandin F2alpha on ovaries in mares.. Prostaglandins 1976 Nov;12(5):881-94.
          pubmed: 988608doi: 10.1016/0090-6980(76)90061-7google scholar: lookup
        16. Drummond A, Ashton B, Buxton S, Cheung M, Cooper A, Heled J, Kearse M, Moir R, Stones-Havas S, Sturrock S, Thierer T, Wilson A. Geneious v5.5. 2011.
        17. Feeney AJ. Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences.. J Exp Med 1990 Nov 1;172(5):1377-90.
          pmc: PMC2188672pubmed: 1700054doi: 10.1084/jem.172.5.1377google scholar: lookup
        18. Flaminio MJ, Rush BR, Davis EG, Hennessy K, Shuman W, Wilkerson MJ. Characterization of peripheral blood and pulmonary leukocyte function in healthy foals.. Vet Immunol Immunopathol 2000 Mar 15;73(3-4):267-85.
          pubmed: 10713340doi: 10.1016/s0165-2427(00)00149-5google scholar: lookup
        19. Ford JE, Home WA, Gibson DM. Light chain isotype regulation in the horse. Characterization of Ig kappa genes.. J Immunol 1994 Aug 1;153(3):1099-111.
          pubmed: 8027543
        20. Fry TJ, Mackall CL. Interleukin-7: from bench to clinic.. Blood 2002 Jun 1;99(11):3892-904.
          pubmed: 12010786doi: 10.1182/blood.v99.11.3892google scholar: lookup
        21. Gibbings DJ, Marcet-Palacios M, Sekar Y, Ng MC, Befus AD. CD8 alpha is expressed by human monocytes and enhances Fc gamma R-dependent responses.. BMC Immunol 2007 Aug 1;8:12.
          pmc: PMC2000912pubmed: 17678538doi: 10.1186/1471-2172-8-12google scholar: lookup
        22. Gontier E, Ayrault O, Godet I, Nau F, Ladevèze V. Developmental progression of immunoglobulin heavy chain diversity in sheep.. Vet Immunol Immunopathol 2005 Jan 10;103(1-2):31-51.
          pubmed: 15626460doi: 10.1016/j.vetimm.2004.08.013google scholar: lookup
        23. Hara S, Diesterbeck US, König S, Czerny CP. Transcriptional analysis of equine λ-light chains in the horse breeds Rhenish-German Coldblood and Hanoverian Warmblood.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):50-65.
          pubmed: 22088675doi: 10.1016/j.vetimm.2011.10.006google scholar: lookup
        24. Hirji N, Lin TJ, Befus AD. A novel CD8 molecule expressed by alveolar and peritoneal macrophages stimulates nitric oxide production.. J Immunol 1997 Feb 15;158(4):1833-40.
          pubmed: 9029123
        25. Hood L, Gray WR, Sanders BG, Dreyer WJ. Light chain evolution. Cold Spring Harb Symp Quant Biol 1967;32:133–146.
        26. Jiang N, Weinstein JA, Penland L, White RA 3rd, Fisher DS, Quake SR. Determinism and stochasticity during maturation of the zebrafish antibody repertoire.. Proc Natl Acad Sci U S A 2011 Mar 29;108(13):5348-53.
          pmc: PMC3069157pubmed: 21393572doi: 10.1073/pnas.1014277108google scholar: lookup
        27. Kastner P, Chan S. PU.1: a crucial and versatile player in hematopoiesis and leukemia.. Int J Biochem Cell Biol 2008;40(1):22-7.
          pubmed: 17374502doi: 10.1016/j.biocel.2007.01.026google scholar: lookup
        28. Kaushik AK, Kehrli ME Jr, Kurtz A, Ng S, Koti M, Shojaei F, Saini SS. Somatic hypermutations and isotype restricted exceptionally long CDR3H contribute to antibody diversification in cattle.. Vet Immunol Immunopathol 2009 Jan 15;127(1-2):106-13.
          pubmed: 19012969doi: 10.1016/j.vetimm.2008.09.024google scholar: lookup
        29. Kelus AS, Weiss S. Variant strain of rabbits lacking immunoglobulin kappa polypeptide chain.. Nature 1977 Jan 13;265(5590):156-8.
          pubmed: 401946doi: 10.1038/265156a0google scholar: lookup
        30. Kent D, Copley M, Benz C, Dykstra B, Bowie M, Eaves C. Regulation of hematopoietic stem cells by the steel factor/KIT signaling pathway.. Clin Cancer Res 2008 Apr 1;14(7):1926-30.
          pubmed: 18381929doi: 10.1158/1078-0432.ccr-07-5134google scholar: lookup
        31. Koschmieder S, Halmos B, Levantini E, Tenen DG. Dysregulation of the C/EBPalpha differentiation pathway in human cancer.. J Clin Oncol 2009 Feb 1;27(4):619-28.
          pmc: PMC2645860pubmed: 19075268doi: 10.1200/jco.2008.17.9812google scholar: lookup
        32. Koti M, Kataeva G, Kaushik AK. Novel atypical nucleotide insertions specifically at VH-DH junction generate exceptionally long CDR3H in cattle antibodies.. Mol Immunol 2010 Jul;47(11-12):2119-28.
          pubmed: 20435350doi: 10.1016/j.molimm.2010.02.014google scholar: lookup
        33. Kydd J, Antczak DF, Allen WR, Barbis D, Butcher G, Davis W, Duffus WP, Edington N, Grünig G, Holmes MA. Report of the First International Workshop on Equine Leucocyte Antigens, Cambridge, UK, July 1991.. Vet Immunol Immunopathol 1994 Jul;42(1):3-60.
          pubmed: 7975180doi: 10.1016/0165-2427(94)90088-4google scholar: lookup
        34. Lafaille JJ, DeCloux A, Bonneville M, Takagaki Y, Tonegawa S. Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining.. Cell 1989 Dec 1;59(5):859-70.
          pubmed: 2590942doi: 10.1016/0092-8674(89)90609-0google scholar: lookup
        35. Lee J, Monson NL, Lipsky PE. The V lambda J lambda repertoire in human fetal spleen: evidence for positive selection and extensive receptor editing.. J Immunol 2000 Dec 1;165(11):6322-33.
          pubmed: 11086069doi: 10.4049/jimmunol.165.11.6322google scholar: lookup
        36. Lefranc MP. Nomenclature of the human immunoglobulin genes.. Curr Protoc Immunol 2001 May;Appendix 1:A.1P.1-A.1P.37.
          pubmed: 18432650doi: 10.1002/0471142735.ima01ps40google scholar: lookup
        37. Lin TJ, Hirji N, Stenton GR, Gilchrist M, Grill BJ, Schreiber AD, Befus AD. Activation of macrophage CD8: pharmacological studies of TNF and IL-1 beta production.. J Immunol 2000 Feb 15;164(4):1783-92.
          pubmed: 10657625doi: 10.4049/jimmunol.164.4.1783google scholar: lookup
        38. Lunn DP, Holmes MA, Antczak DF, Agerwal N, Baker J, Bendali-Ahcene S, Blanchard-Channell M, Byrne KM, Cannizzo K, Davis W, Hamilton MJ, Hannant D, Kondo T, Kydd JH, Monier MC, Moore PF, O'Neil T, Schram BR, Sheoran A, Stott JL, Sugiura T, Vagnoni KE. Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California, July 1995.. Vet Immunol Immunopathol 1998 Mar 31;62(2):101-43.
          pubmed: 9638857doi: 10.1016/s0165-2427(97)00160-8google scholar: lookup
        39. Martin BR, Larson KA. Immune response of equine fetus to coliphage T2.. Am J Vet Res 1973 Oct;34(10):1363-4.
          pubmed: 4748249
        40. McNiece IK, Langley KE, Zsebo KM. The role of recombinant stem cell factor in early B cell development. Synergistic interaction with IL-7.. J Immunol 1991 Jun 1;146(11):3785-90.
          pubmed: 1709662
        41. Miqueu P, Guillet M, Degauque N, Doré JC, Soulillou JP, Brouard S. Statistical analysis of CDR3 length distributions for the assessment of T and B cell repertoire biases.. Mol Immunol 2007 Feb;44(6):1057-64.
          pubmed: 16930714doi: 10.1016/j.molimm.2006.06.026google scholar: lookup
        42. Montecino-Rodriguez E, Dorshkind K. New perspectives in B-1 B cell development and function.. Trends Immunol 2006 Sep;27(9):428-33.
          pubmed: 16861037doi: 10.1016/j.it.2006.07.005google scholar: lookup
        43. Morgan DO, Bryans JT, Mock RE. Immunoglobulins produced by the antigenized equine fetus.. J Reprod Fertil Suppl 1975 Oct;(23):735-8.
          pubmed: 1060874
        44. Nagasawa T. Microenvironmental niches in the bone marrow required for B-cell development.. Nat Rev Immunol 2006 Feb;6(2):107-16.
          pubmed: 16491135doi: 10.1038/nri1780google scholar: lookup
        45. Nagasawa T, Hirota S, Tachibana K, Takakura N, Nishikawa S, Kitamura Y, Yoshida N, Kikutani H, Kishimoto T. Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1.. Nature 1996 Aug 15;382(6592):635-8.
          pubmed: 8757135doi: 10.1038/382635a0google scholar: lookup
        46. Nielsen JS, McNagny KM. CD34 is a key regulator of hematopoietic stem cell trafficking to bone marrow and mast cell progenitor trafficking in the periphery.. Microcirculation 2009 Aug;16(6):487-96.
          pubmed: 19479621doi: 10.1080/10739680902941737google scholar: lookup
        47. Parrish CR, Carmichael LE, Antczak DF. Antigenic relationships between canine parvovirus type 2, feline panleukopenia virus and mink enteritis virus using conventional antisera and monoclonal antibodies.. Arch Virol 1982;72(4):267-78.
          pubmed: 6180709doi: 10.1007/bf01315223google scholar: lookup
        48. Pascual V, Verkruyse L, Casey ML, Capra JD. Analysis of Ig H chain gene segment utilization in human fetal liver. Revisiting the "proximal utilization hypothesis".. J Immunol 1993 Oct 15;151(8):4164-72.
          pubmed: 8409393
        49. Perryman LE, McGuire TC, Torbeck RL. Ontogeny of lymphocyte function in the equine fetus.. Am J Vet Res 1980 Aug;41(8):1197-200.
          pubmed: 6969560
        50. Pinheiro A, Lanning D, Alves PC, Mage RG, Knight KL, van der Loo W, Esteves PJ. Molecular bases of genetic diversity and evolution of the immunoglobulin heavy chain variable region (IGHV) gene locus in leporids.. Immunogenetics 2011 Jul;63(7):397-408.
          pmc: PMC3404511pubmed: 21594770doi: 10.1007/s00251-011-0533-9google scholar: lookup
        51. Pridans C, Holmes ML, Polli M, Wettenhall JM, Dakic A, Corcoran LM, Smyth GK, Nutt SL. Identification of Pax5 target genes in early B cell differentiation.. J Immunol 2008 Feb 1;180(3):1719-28.
          pubmed: 18209069doi: 10.4049/jimmunol.180.3.1719google scholar: lookup
        52. Reynaud CA, Garcia C, Hein WR, Weill JC. Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process.. Cell 1995 Jan 13;80(1):115-25.
          pubmed: 7813007doi: 10.1016/0092-8674(95)90456-5google scholar: lookup
        53. Reynaud CA, Dahan A, Anquez V, Weill JC. Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region.. Cell 1989 Oct 6;59(1):171-83.
          pubmed: 2507167doi: 10.1016/0092-8674(89)90879-9google scholar: lookup
        54. Rothenberg EV. T cell lineage commitment: identity and renunciation.. J Immunol 2011 Jun 15;186(12):6649-55.
          pmc: PMC3111953pubmed: 21646301doi: 10.4049/jimmunol.1003703google scholar: lookup
        55. Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers.. Methods Mol Biol 2000;132:365-86.
          pubmed: 10547847doi: 10.1385/1-59259-192-2:365google scholar: lookup
        56. Saini SS, Kaushik A. Extensive CDR3H length heterogeneity exists in bovine foetal VDJ rearrangements.. Scand J Immunol 2002 Feb;55(2):140-8.
        57. Sanz I. Multiple mechanisms participate in the generation of diversity of human H chain CDR3 regions.. J Immunol 1991 Sep 1;147(5):1720-9.
          pubmed: 1908883
        58. Shimanuki M, Sonoki T, Hosoi H, Watanuki J, Murata S, Kawakami K, Matsuoka H, Hanaoka N, Nakakuma H. Molecular cloning of IGλ rearrangements using long-distance inverse PCR (LDI-PCR).. Eur J Haematol 2013 Jan;90(1):59-67.
          pubmed: 23113889doi: 10.1111/ejh.12037google scholar: lookup
        59. Shiokawa S, Mortari F, Lima JO, Nuñez C, Bertrand FE 3rd, Kirkham PM, Zhu S, Dasanayake AP, Schroeder HW Jr. IgM heavy chain complementarity-determining region 3 diversity is constrained by genetic and somatic mechanisms until two months after birth.. J Immunol 1999 May 15;162(10):6060-70.
          pubmed: 10229847
        60. Sinkora J, Reháková Z, Sinkora M, Cukrowska B, Tlaskalová-Hogenová H, Bianchi AT, De Geus B. Expression of CD2 on porcine B lymphocytes.. Immunology 1998 Nov;95(3):443-9.
        61. Sinkora M, Sinkorova J, Butler JE. B cell development and VDJ rearrangement in the fetal pig.. Vet Immunol Immunopathol 2002 Sep 10;87(3-4):341-6.
          pubmed: 12072256doi: 10.1016/s0165-2427(02)00062-4google scholar: lookup
        62. Souto-Carneiro MM, Sims GP, Girschik H, Lee J, Lipsky PE. Developmental changes in the human heavy chain CDR3.. J Immunol 2005 Dec 1;175(11):7425-36.
          pubmed: 16301650doi: 10.4049/jimmunol.175.11.7425google scholar: lookup
        63. Sun Y, Wang C, Wang Y, Zhang T, Ren L, Hu X, Zhang R, Meng Q, Guo Y, Fei J, Li N, Zhao Y. A comprehensive analysis of germline and expressed immunoglobulin repertoire in the horse.. Dev Comp Immunol 2010 Sep;34(9):1009-20.
          pubmed: 20466019doi: 10.1016/j.dci.2010.05.003google scholar: lookup
        64. Tallmadge RL, Tseng CT, Felippe MJ. Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse.. Dev Comp Immunol 2014 Oct;46(2):171-9.
          pmc: PMC4107094pubmed: 24726757doi: 10.1016/j.dci.2014.04.001google scholar: lookup
        65. Tallmadge RL, Tseng CT, King RA, Felippe MJ. Developmental progression of equine immunoglobulin heavy chain variable region diversity.. Dev Comp Immunol 2013 Sep;41(1):33-43.
          pmc: PMC3672396pubmed: 23567345doi: 10.1016/j.dci.2013.03.020google scholar: lookup
        66. Tallmadge RL, McLaughlin K, Secor E, Ruano D, Matychak MB, Flaminio MJ. Expression of essential B cell genes and immunoglobulin isotypes suggests active development and gene recombination during equine gestation.. Dev Comp Immunol 2009 Sep;33(9):1027-38.
          pubmed: 19442687doi: 10.1016/j.dci.2009.05.002google scholar: lookup
        67. Timens W, Kamps WA. Hemopoiesis in human fetal and embryonic liver.. Microsc Res Tech 1997 Dec 1;39(5):387-97.
        68. Tonegawa S. Somatic generation of antibody diversity.. Nature 1983 Apr 14;302(5909):575-81.
          pubmed: 6300689doi: 10.1038/302575a0google scholar: lookup
        69. Tsiftsoglou AS, Vizirianakis IS, Strouboulis J. Erythropoiesis: model systems, molecular regulators, and developmental programs.. IUBMB Life 2009 Aug;61(8):800-30.
          pubmed: 19621348doi: 10.1002/iub.226google scholar: lookup
        70. Verma S, Aitken R. Somatic hypermutation leads to diversification of the heavy chain immunoglobulin repertoire in cattle.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):14-22.
          pubmed: 22070825doi: 10.1016/j.vetimm.2011.10.001google scholar: lookup
        71. Wang H, Morse HC 3rd. IRF8 regulates myeloid and B lymphoid lineage diversification.. Immunol Res 2009;43(1-3):109-17.
          pmc: PMC2803682pubmed: 18806934doi: 10.1007/s12026-008-8055-8google scholar: lookup
        72. Wertz N, Vazquez J, Wells K, Sun J, Butler JE. Antibody repertoire development in fetal and neonatal piglets. XII. Three IGLV genes comprise 70% of the pre-immune repertoire and there is little junctional diversity.. Mol Immunol 2013 Oct;55(3-4):319-28.
          pubmed: 23570908doi: 10.1016/j.molimm.2013.03.012google scholar: lookup
        73. Wu TT, Kabat EA. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity.. J Exp Med 1970 Aug 1;132(2):211-50.
          pmc: PMC2138737pubmed: 5508247doi: 10.1084/jem.132.2.211google scholar: lookup
        74. Xu JL, Davis MM. Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities.. Immunity 2000 Jul;13(1):37-45.
          pubmed: 10933393doi: 10.1016/s1074-7613(00)00006-6google scholar: lookup
        75. Yancopoulos GD, Desiderio SV, Paskind M, Kearney JF, Baltimore D, Alt FW. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines.. Nature 1984 Oct 25-31;311(5988):727-33.
          pubmed: 6092962doi: 10.1038/311727a0google scholar: lookup
        76. Yokota T, Huang J, Tavian M, Nagai Y, Hirose J, Zúñiga-Pflücker JC, Péault B, Kincade PW. Tracing the first waves of lymphopoiesis in mice.. Development 2006 May;133(10):2041-51.
          pubmed: 16611687doi: 10.1242/dev.02349google scholar: lookup
        77. Zemlin M, Bauer K, Hummel M, Pfeiffer S, Devers S, Zemlin C, Stein H, Versmold HT. The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage.. Blood 2001 Mar 1;97(5):1511-3.
          pubmed: 11222402doi: 10.1182/blood.v97.5.1511google scholar: lookup

        Citations

        This article has been cited 7 times.
        1. Boettcher AN, Li Y, Ahrens AP, Kiupel M, Byrne KA, Loving CL, Cino-Ozuna AG, Wiarda JE, Adur M, Schultz B, Swanson JJ, Snella EM, Ho CS, Charley SE, Kiefer ZE, Cunnick JE, Putz EJ, Dell'Anna G, Jens J, Sathe S, Goldman F, Westin ER, Dekkers JCM, Ross JW, Tuggle CK. Novel Engraftment and T Cell Differentiation of Human Hematopoietic Cells in ART(-/-)IL2RG(-/Y) SCID Pigs.. Front Immunol 2020;11:100.
          doi: 10.3389/fimmu.2020.00100pubmed: 32117254google scholar: lookup
        2. Zhang W, Ye L, Wang F, Zheng J, Tian X, Chen Y, Ding G, Yang Z. Immunomodulatory Effects of the Meretrix Meretrix Oligopeptide (QLNWD) on Immune-Deficient Mice.. Molecules 2019 Dec 5;24(24).
          doi: 10.3390/molecules24244452pubmed: 31817348google scholar: lookup
        3. Boettcher AN, Loving CL, Cunnick JE, Tuggle CK. Development of Severe Combined Immunodeficient (SCID) Pig Models for Translational Cancer Modeling: Future Insights on How Humanized SCID Pigs Can Improve Preclinical Cancer Research.. Front Oncol 2018;8:559.
          doi: 10.3389/fonc.2018.00559pubmed: 30560086google scholar: lookup
        4. Tallmadge RL, Žygelytė E, Van de Walle GR, Kristie TM, Felippe MJB. Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 Activity In Vitro.. Front Vet Sci 2018;5:34.
          doi: 10.3389/fvets.2018.00034pubmed: 29594155google scholar: lookup
        5. Schwab UE, Tallmadge RL, Matychak MB, Felippe MJB. Effects of autologous stromal cells and cytokines on differentiation of equine bone marrow-derived progenitor cells.. Am J Vet Res 2017 Oct;78(10):1215-1228.
          doi: 10.2460/ajvr.78.10.1215pubmed: 28945121google scholar: lookup
        6. Tallmadge RL, Miller SC, Parry SA, Felippe MJB. Antigen-specific immunoglobulin variable region sequencing measures humoral immune response to vaccination in the equine neonate.. PLoS One 2017;12(5):e0177831.
          doi: 10.1371/journal.pone.0177831pubmed: 28520789google scholar: lookup
        7. Prieto JMB, Tallmadge RL, Felippe MJB. Developmental expression of B cell molecules in equine lymphoid tissues.. Vet Immunol Immunopathol 2017 Jan;183:60-71.
          doi: 10.1016/j.vetimm.2016.12.004pubmed: 28063478google scholar: lookup