Expression of essential B cell genes and immunoglobulin isotypes suggests active development and gene recombination during equine gestation

Tallmadge, Rebecca L.; McLaughlin, Kristin; Secor, Erica J.; Ruano, Diana; Matychak, Mary Beth; Flaminio, M. Julia B.F.

doi:10.1016/j.dci.2009.05.002

Cited by 30 publications

(48 citation statements)

References 67 publications

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“…In other studies, administration of a Venezuelan equine encephalomyelitis antigen to equine fetuses between 232 and 283 days of gestational age resulted in serum neutralization titers higher than those elicited by the same preparation in adult horses (18,19). Recent work supports these findings, showing that active B-cell development and immunoglobulin isotype switching occur during equine gestation and the neonatal period (27). Proliferation of peripheral blood lymphocytes in response to mitogens is slightly reduced at birth but rapidly increases to adult levels (6,25).…”

supporting

confidence: 62%

Equine Neonates Have Attenuated Humoral and Cell-Mediated Immune Responses to a Killed Adjuvanted Vaccine Compared to Adult Horses

Ryan

Giguère

2010

Clin Vaccine Immunol

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The objectives of this study were to compare relative vaccine-specific serum immunoglobulin concentrations, vaccine-specific lymphoproliferative responses, and cytokine profiles of proliferating lymphocytes between 3-day-old foals, 3-month-old foals, and adult horses after vaccination with a killed adjuvanted vaccine. Horses were vaccinated intramuscularly twice at 3-week intervals with a vaccine containing antigens from bovine viral respiratory pathogens to avoid interference from maternal antibody. Both groups of foals and adult horses responded to the vaccine with a significant increase in vaccine-specific IgGa and IgG(T) concentrations. In contrast, only adult horses and 3-month-old foals mounted significant vaccine-specific total IgG, IgGb, and IgM responses. Vaccine-specific concentrations of IgM and IgG(T) were significantly different between all groups, with the highest concentrations occurring in adult horses, followed by 3-month-old foals and, finally, 3-day-old foals. Only the adult horses mounted significant vaccine-specific lymphoproliferative responses. Baseline gamma interferon (IFN-␥) and interleukin-4 (IL-4) concentrations

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supporting

confidence: 62%

Equine Neonates Have Attenuated Humoral and Cell-Mediated Immune Responses to a Killed Adjuvanted Vaccine Compared to Adult Horses

Ryan

Giguère

2010

Clin Vaccine Immunol

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“…In our study, we measured only serum IgA but there is no reason to believe that secretory IgA levels would not correlate with serum levels in horses. Studies carried out by others have validated measurement of serum IgA as a parameter to evaluate immunity of horses (Foote et al, 2005;Tallmadge et al, 2009). Moreover, in a recent study involving horses with common variable immunodeficiency (CVID), the authors noticed a decline in serum IgA concentrations that correlated with worsening of the clinical symptoms.…”

Section: Discussionmentioning

confidence: 98%

Lower serum IgA levels in horses kept under intensive sanitary management and physical training

Souza

Miotto

Bonin

et al. 2010

Animal

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Quantity and variety of environmental antigens, age, diet, vaccine protocols, exercising practice and mucosal cytokine microenvironment are factors that influence serum immunoglobulin (Ig) levels. IgA, IgG, IgG(T) and IgM were quantified in 60 horses, which were classified into two groups, 'intensive' or 'relaxed', according to sanitary standards of the facilities and physical exercise to which animals were subjected to. The 'intensive' group presented lower means for all isotypes, but only IgA presented a significant (P , 0.0064) difference when compared to the 'relaxed' group. This suggests that mucosal immunity found in the 'intensive' group is lower when compared to the 'relaxed' group. Our data suggest that athlete horses may be less poised to mount an effective mucosal immunity response to environmental challenges and should not be considered by the same perspectives as a free-ranging horse.

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“…In the absence of endogenous production, serum IgM concentrations decrease over time, as we observed in the FPS-affected but not in the unaffected Fell Pony foals. The equine fetus produces IgM during gestation and may be born with serum IgM concentrations of 10 to 25 mg/dl (66). Of note, FPS1 postsuckling serum IgM concentrations close to birth were within the range observed for healthy Fell Pony foals, likely due to colostral transfer.…”

Section: Discussionmentioning

confidence: 97%

“…In contrast, in fetal pigs, B cells are detected in the bone marrow and spleen approximately 2 weeks after their appearance in the liver, by day 45 of the 114-day gestation (62). Studies in our laboratory have demonstrated that B lymphopoiesis and Ig gene recombination are active during equine fetal life, as with B lymphopoiesis in fetal pigs (66). At 90 to 120 days (approximately one-third of the 330-to 340-day gestation), genes essential for B cell development, including CD20, CD21, CD22, CD27, CD40, CD40LG, PTPRC/B220, CD79A, CD79B, RAG-2, IGHM, IGHD, IGHA, and IGHG isotypes and the lambda light-chain IGLC gene, are expressed in the liver, bone marrow, and spleen.…”

mentioning

confidence: 90%

Fell Pony Syndrome: Characterization of Developmental Hematopoiesis Failure and Associated Gene Expression Profiles

Tallmadge

Stokol

Gould-Earley

et al. 2012

Clin. Vaccine Immunol.

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c Fell Pony syndrome (FPS) is a fatal immunodeficiency that occurs in foals of the Fell Pony breed. Affected foals present with severe anemia, B cell lymphopenia, and opportunistic infections. Our objective was to conduct a prospective study of potential FPS-affected Fell Pony foals to establish clinical, immunological, and molecular parameters at birth and in the first few weeks of life. Complete blood counts, peripheral blood lymphocyte phenotyping, and serum immunoglobulin concentrations were determined for 3 FPS-affected foals, 49 unaffected foals, and 6 adult horses. In addition, cytology of bone marrow aspirates was performed sequentially in a subset of foals. At birth, the FPS-affected foals were not noticeably ill and had hematocrit and circulating B cell counts comparable to those of unaffected foals; however, over 6 weeks, values for both parameters steadily declined. A bone marrow aspirate from a 3-week-old FPS-affected foal revealed erythroid hyperplasia and concurrent erythroid and myeloid dysplasia, which progressed to a severe erythroid hypoplasia at 5 weeks of life. Immunohistochemical staining confirmed the paucity of B cells in primary and secondary lymphoid tissues. The mRNA expression of genes involved in B cell development, signaling, and maturation was investigated using qualitative and quantitative reverse transcriptase PCR (RT-PCR). Several genes, including CREB1, EP300, MYB, PAX5, and SPI1/PU.1, were sequenced from FPS-affected and unaffected foals. Our study presents evidence of fetal erythrocyte and B cell hematopoiesis with rapid postnatal development of anemia and B lymphopenia in FPS-affected foals. The transition between fetal/neonatal and adult-like hematopoiesis may be an important aspect of the pathogenesis of FPS.

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Expression of essential B cell genes and immunoglobulin isotypes suggests active development and gene recombination during equine gestation

Cited by 30 publications

References 67 publications

Equine Neonates Have Attenuated Humoral and Cell-Mediated Immune Responses to a Killed Adjuvanted Vaccine Compared to Adult Horses

Equine Neonates Have Attenuated Humoral and Cell-Mediated Immune Responses to a Killed Adjuvanted Vaccine Compared to Adult Horses

Lower serum IgA levels in horses kept under intensive sanitary management and physical training

Fell Pony Syndrome: Characterization of Developmental Hematopoiesis Failure and Associated Gene Expression Profiles

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