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Molecular immunology2012; 51(2); 169-176; doi: 10.1016/j.molimm.2012.03.018

Expression of essential B cell development genes in horses with common variable immunodeficiency.

Abstract: Common variable immunodeficiency (CVID) is a heterogeneous disorder of B cell differentiation or function with inadequate antibody production. Our laboratory studies a natural form of CVID in horses characterized by late-onset B cell lymphopenia due to impaired B cell production in the bone marrow. This study was undertaken to assess the status of B cell differentiation in the bone marrow of CVID-affected horses by measuring the expression of genes essential for early B cell commitment and development. Standard RT-PCR revealed that most of the transcription factors and key signaling molecules that directly regulate B cell differentiation in the bone marrow and precede PAX5 are expressed in the affected horses. Yet, the expression of PAX5 and relevant target genes was variable. Quantitative RT-PCR analysis confirmed that the mRNA expression of E2A, PAX5, CD19, and IGHD was significantly reduced in equine CVID patients when compared to healthy horses (p<0.05). In addition, the PAX5/EBF1 and PAX5/B220 ratios were significantly reduced in CVID patients (p<0.01). Immunohistochemical analysis confirmed the absence of PAX5-BSAP expression in the bone marrow of affected horses. Our data suggest that B cell development seems to be impaired at the transition between pre-pro-B cells and pro-B cells in equine CVID patients.
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Publication Date: 2012-03-30 PubMed ID: 22464097PubMed Central: PMC3351080DOI: 10.1016/j.molimm.2012.03.018Google 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 research dives into the investigation of gene expression associated with B cell development in horses affected by Common Variable Immunodeficiency (CVID), a disorder characterized by diminished antibody production. The findings showed that the expression of certain genes crucial for early B cell development was significantly reduced in affected horses, suggesting that B cell development might be impaired between two stages of differentiation: pre-pro-B cells and pro-B cells.

Understanding CVID in Horses

  • This study centered largely on horses suffering from a naturally occurring form of Common Variable Immunodeficiency (CVID). The affliction is a diverse disorder that hinders B cell differentiation – the process by which cells become specialized – or function, leading to inadequate production of antibodies.
  • In horses, this disease manifests as B cell lymphopenia that sets in late, predominantly due to impaired B cell production in the bone marrow.

Examining B cell Differentiation

  • The main aim of the study was to assess the status of B cell differentiation in the bone marrow of horses suffering from CVID. This was achieved by monitoring the expression of those genes that are crucial for early B cell development and commitment.
  • The researchers found most transcription factors and vital signaling molecules that directly control B cell differentiation within the bone marrow and that are expressed before the PAX5 gene were expressed in CVID-affected horses.
  • However, the expression of PAX5 and relevant target genes was inconsistent.

Reduced Gene Expression and Impaired B Cell Development

  • Quantitative RT-PCR analysis substantiated that mRNA expression for genes E2A, PAX5, CD19, and IGHD was markedly lower in horses with CVID compared to healthy horses. This difference was statistically significant (p<0.05).
  • The ratios of PAX5/EBF1 and PAX5/B220 – two critical parameters – were also found to be significantly lower in CVID patients (p<0.01).
  • Immunohistochemical analysis further verified the lack of PAX5-BSAP expression in the bone marrow of affected horses.
  • Based on these findings, it may be implied that the development of B cells is likely hindered at the transition stage between pre-pro-B cells and pro-B cells in equine CVID patients.

Cite This Article

APA
Tallmadge RL, Such KA, Miller KC, Matychak MB, Felippe MJ. (2012). Expression of essential B cell development genes in horses with common variable immunodeficiency. Mol Immunol, 51(2), 169-176. https://doi.org/10.1016/j.molimm.2012.03.018

Publication

Molecular immunology
ISSN: 1872-9142
NlmUniqueID: 7905289
Country: England
Language: English
Volume: 51
Issue: 2
Pages: 169-176

Researcher Affiliations

Tallmadge, R L
  • Equine Immunology Lab, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. rlt8@cornell.edu
Such, K A
    Miller, K C
      Matychak, M B
        Felippe, M J B

          MeSH Terms

          • Animals
          • B-Lymphocytes / cytology
          • B-Lymphocytes / immunology
          • Bone Marrow Cells / cytology
          • Bone Marrow Cells / immunology
          • Cell Differentiation / genetics
          • Cell Differentiation / immunology
          • Common Variable Immunodeficiency / genetics
          • Common Variable Immunodeficiency / immunology
          • Common Variable Immunodeficiency / veterinary
          • Horses
          • Immunohistochemistry
          • PAX5 Transcription Factor / genetics
          • Precursor Cells, B-Lymphoid / cytology
          • Precursor Cells, B-Lymphoid / immunology
          • Real-Time Polymerase Chain Reaction
          • Reverse Transcriptase Polymerase Chain Reaction

          Grant Funding

          • R03AI079796 / NIAID NIH HHS
          • DP2OD007216 / NIH HHS
          • DP2 OD007216 / NIH HHS
          • R03 AI079796-01 / NIAID NIH HHS
          • R03 AI079796 / NIAID NIH HHS
          • R03 AI079796-02 / NIAID NIH HHS
          • DP2 OD007216-01 / NIH HHS

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          Citations

          This article has been cited 6 times.
          1. Pecoraro HL, Felippe MJB, Miller AD, Divers TJ, Simpson KW, Guyer KM, Duhamel GE. Neuroborreliosis in a horse with common variable immunodeficiency. J Vet Diagn Invest 2019 Mar;31(2):241-245.
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          2. Ameratunga R, Koopmans W, Woon ST, Leung E, Lehnert K, Slade CA, Tempany JC, Enders A, Steele R, Browett P, Hodgkin PD, Bryant VL. Epistatic interactions between mutations of TACI (TNFRSF13B) and TCF3 result in a severe primary immunodeficiency disorder and systemic lupus erythematosus. Clin Transl Immunology 2017 Oct;6(10):e159.
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          3. Prieto JMB, Tallmadge RL, Felippe MJB. Developmental expression of B cell molecules in equine lymphoid tissues. Vet Immunol Immunopathol 2017 Jan;183:60-71.
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          4. Badial PR, Tallmadge RL, Miller S, Stokol T, Richards K, Borges AS, Felippe MJ. Applied Protein and Molecular Techniques for Characterization of B Cell Neoplasms in Horses. Clin Vaccine Immunol 2015 Nov;22(11):1133-45.
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          5. Tallmadge RL, Shen L, Tseng CT, Miller SC, Barry J, Felippe MJ. Bone marrow transcriptome and epigenome profiles of equine common variable immunodeficiency patients unveil block of B lymphocyte differentiation. Clin Immunol 2015 Oct;160(2):261-76.
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