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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.
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Publication Date: 2014-09-02 PubMed ID: 25179685PubMed Central: PMC4198492DOI: 10.1007/s00251-014-0799-9Google Scholar: Lookup
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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

Immunogenetics
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

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