Topic:B cells
B cells are a type of white blood cell found in horses that are integral to the adaptive immune system. They originate from the bone marrow and are responsible for producing antibodies, which are proteins that bind to specific antigens to neutralize pathogens such as bacteria and viruses. B cells also play a role in antigen presentation and the activation of other immune cells. In equine health, the study of B cells includes understanding their development, function, and response to infections and vaccinations. This page compiles peer-reviewed research studies and scholarly articles that explore the biology, regulation, and clinical implications of B cells in horses, contributing to a deeper understanding of equine immunology.
Applied Protein and Molecular Techniques for Characterization of B Cell Neoplasms in Horses. Mature B cell neoplasms cover a spectrum of diseases involving lymphoid tissues (lymphoma) or blood (leukemia), with an overlap between these two presentations. Previous studies describing equine lymphoid neoplasias have not included analyses of clonality using molecular techniques. The objective of this study was to use molecular techniques to advance the classification of B cell lymphoproliferative diseases in five adult equine patients with a rare condition of monoclonal gammopathy, B cell leukemia, and concurrent lymphadenopathy (lymphoma/leukemia). The B cell neoplasms were phenotypically...
Suspected malignant transformation of B lymphocytes in the equine cornea from immune-mediated keratitis. To describe clinical, in vivo confocal microscopic, histopathologic, polymerase chain reaction assay for antigen receptor rearrangement (PARR) and immunohistochemical features of a horse with suspected malignant transformation of corneal B lymphocytes in immune-mediated keratitis (IMMK) and to also report surgical management and adjunctive treatment including topical and radiation therapies. Methods: A 15-year-old Oldenburg gelding was examined for presumptive progressive stromal IMMK of the right eye which became refractory to medical management. Corneal in vivo confocal microscopy revealed...
Humoral and cell-mediated immune response, and growth factor synthesis after direct intraarticular injection of rAAV2-IGF-I and rAAV5-IGF-I in the equine middle carpal joint. Intraarticular (IA) administration of viral vectors expressing a therapeutic transgene is an attractive treatment modality for osteoarthritis (OA) as the joint can be treated as a contained unit. Humoral and cell-mediated immune responses in vivo can limit vector effectiveness. Transduction of articular tissues has been investigated; however, the immune response to IA vectors remains largely unknown. We hypothesized that IA rAAV2 and rAAV5 overexpressing insulin-like growth factor-I (IGF-I) would result in long-term IGF-I formation but would also induce neutralizing antibodies (NAb) and anti-c...
Classification and clinical features in 88 cases of equine cutaneous lymphoma. Equine cutaneous lymphoma is an uncommon disease that can present with variable clinical signs, immunosuppression, and rapid systemic disease progression. Various subtypes of equine lymphoma have been described and classified according to a veterinary adaptation of the World Health Organization classification system, but little data is available regarding the association between lymphoma subtypes and epidemiological criteria and/or clinical outcome. The objective of the current study was to classify previously diagnosed cases of equine cutaneous lymphoma and correlate subtypes with clinical da...
Clinical trials of immunogene therapy for spontaneous tumors in companion animals. Despite the important progress obtained in the treatment of some pets' malignancies, new treatments need to be developed. Being critical in cancer control and progression, the immune system's appropriate modulation may provide effective therapeutic options. In this review we summarize the outcomes of published immunogene therapy veterinary clinical trials reported by many research centers. A variety of tumors such as canine melanoma, soft tissue sarcomas, osteosarcoma and lymphoma, feline fibrosarcoma, and equine melanoma were subjected to different treatment approaches. Both viral and mainly ...
Development of an in vitro model system for studying the interaction of Equus caballus IgE with its high-affinity receptor FcεRI. The interaction of IgE with its high-affinity Fc receptor (FcεRI) followed by an antigenic challenge is the principal pathway in IgE mediated allergic reactions. As a consequence of the high affinity binding between IgE and FcεRI, along with the continuous production of IgE by B cells, allergies usually persist throughout life, with currently no permanent cure available. Horses, especially race horses, which are commonly inbred, are a species of mammals that are very prone to the development of hypersensitivity responses, which can seriously affect their performance. Physiological responses ...
[Equine leukaemic lymphoma–a rare form of equine lymphoma]. Equine leukaemic lymphoma is a rare disease of the haematopoetic tissue. It results from neoplastic degradation of B- and T-lymphocytes and their occurrence in the blood. Clinical signs are often unspecific and include chronic weight loss, ventral oedema at the thorax and abdomen and regional lymphadenopathy. Horses are often presented late in the course of the disease and therapy is rarely successful. This review summarizes the clinical pathologic findings of equine leukaemic lymphoma and the findings of laboratory testing and other diagnostic measures, and presents treatment options describe...
Hematopoiesis in the equine fetal liver suggests immune preparedness. 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)...
Pathology of fatal lineage 1 and 2 West Nile virus infections in horses in South Africa. Since 2007, West Nile virus (WNV) has been reported in South African horses, causing severe neurological signs. All cases were of lineage 2, except for one case that clustered with lineage 1 viruses. In the present study, gross and microscopic lesions of six South African lineage 2-infected horses and the one lineage 1 case are described. Diagnoses were confirmed by real-time reverse-transcriptase polymerase chain reaction (RT-PCR) of central nervous system (CNS) tissue and one by RT-PCR of a brain virus isolate. The CNS of all cases was negative by RT-PCR or immunohistochemistry (IHC) for Afr...
Nasal and ocular amyloidosis in a 15-year-old horse. Localized nasal, conjunctival and corneal amyloidosis was diagnosed in a 15-year-old pony with nasal and conjunctival masses and severe dyspnoea. Multiple swellings had been evident in the nostrils for at least two years and had gradually increased in size before presentation due to dyspnoea and exercise intolerance. Surgical debulking of the masses was performed and histological examination revealed large amounts of extracellular, hyaline, eosinophilic, Congo red positive material in the lamina propria of the nasal mucosa. A tentative diagnosis of localized nasal amyloidosis was made. The tre...
Neurolymphomatosis in three horses with multicentric T-cell-rich B-cell lymphoma. Neurolymphomatosis is a rare manifestation of lymphoma and is characterized by neoplastic infiltration of the peripheral nervous system. The present report describes neoplastic infiltration of peripheral nerves in three horses with multicentric lymphoma. Immunohistochemistry revealed the presence of CD79a(+) lymphoblastic cells and well-differentiated CD3(+) T cells, characteristic of T-cell-rich B-cell lymphoma in all cases. Nerve infiltration by lymphoma is rare, but should be considered as a differential diagnosis for peripheral neuropathy in horses with lymphoma.
Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse. To further studies of neonatal immune responses to pathogens and vaccination, we investigated the dynamics of B lymphocyte development and immunoglobulin (Ig) gene diversity. Previously we demonstrated that equine fetal Ig VDJ sequences exhibit combinatorial and junctional diversity levels comparable to those of adult Ig VDJ sequences. Herein, RACE clones from fetal, neonatal, foal, and adult lymphoid tissue were assessed for Ig lambda light chain combinatorial, junctional, and sequence diversity. Remarkably, more lambda variable genes (IGLV) were used during fetal life than later stages and I...
Equine adipose-derived stem cell (ASC) expresses BAFF and its receptors, which may be associated with the differentiation process of ASC towards adipocyte. B cell activating factor (BAFF) and its receptors were regarded as elements of the immune system, regulating the fate of B cell. In recent years, these molecules were identified in a number of normal and pathological tissues, expanding their potential functions beyond the immune system. In this study, on the basis of molecular clone and prokaryotic expression of equine BAFF, we reported that equine adipose-derived stem cell (ASC) expressed BAFF and its receptors, which exhibited the increased expression during ASC adipogenic differentiation in vitro. Moreover, with the addition of recombinant ...
Molecular characterization and evolutionary analysis of horse BAFF-R, a tumor necrosis factor receptor related to B-cell survival. B-cell survival depends on signals induced by B-cell activating factor (BAFF) that binds to the BAFF receptor (BAFF-R). Herein, a BAFF-R homolog was identified in a horse (Equus caballus). The horse BAFF-R gene, located on chromosome 28, spans 1444 base pairs and encodes a 183-amino acid protein. The protein is structurally conserved, in which the DxL motif plays an important role in binding to BAFF. Furthermore, the horse BAFF-R extracellular domain was expressed and purified, which specifically bound to His6-sBAFF and had the capability of blocking the function of His6-sBAFF in vitro. Finall...
Humoral response and antiviral cytokine expression following vaccination of thoroughbred weanlings–a blinded comparison of commercially available vaccines. Previous studies in experimental ponies using interferon gamma (IFN-γ) as a marker for cell mediated immune (CMI) response demonstrated an increase in IFN-γ gene expression following vaccination with an ISCOM subunit, a canarypox recombinant and more recently, an inactivated whole virus vaccine. The objective of this study was to carry out an independent comparison of both humoral antibody and CMI responses elicited following vaccination with all these vaccine presentation systems. Antibody response of 44 Thoroughbred weanlings was monitored for three weeks following the second dose of prima...
B-cell multicentric lymphoma as a probable cause of abortion in a Quarter horse broodmare. A 5-year-old Quarter horse broodmare was evaluated for inappetence, depression, and diarrhea 13 days after aborting a 9-month gestation fetus. Clinical and laboratory examination ruled out uterine rupture and peritonitis. Ultrasonography of the uterus combined with cytological analysis of peritoneal fluid suggested the existence of diffuse lymphoma. A multicentric B-cell lymphoma involving the uterus and ovary was confirmed at necropsy and histopathological examination. Lymhome multicentrique à cellules B comme cause possible d’avortement chez une jument poulinière Quarter Horse. Une jumen...
Characterization of the inflammatory infiltrate and cytokine expression in the skin of horses with recurrent urticaria. Recurrent urticaria (RU) is a common skin disease of horses, but little is known about its pathogenesis. Objective: The aim of this study was to characterize the inflammatory cell infiltrate and cytokine expression pattern in the skin of horses with RU. Methods: Biopsies of lesional and nonlesional skin of horses with RU (n = 8) and of skin from healthy control horses (n = 8) were evaluated. Methods: The inflammatory cell infiltrate was analysed by routine histology. Immunohistochemistry was used to identify T cells (CD3), B ells (CD79), macrophages (MAC387) and mast cells (tryptase). E...
Lymphoma risk in livestock farmers: results of the Epilymph study. We explored the risk of lymphoma and its most prevalent subtypes associated with occupational contact with livestock, and whether risk was modified by age at first contact, in 2,348 incident lymphoma cases and 2,462 controls who participated in the EPILYMPH case-control study. A detailed occupational history was collected in cases and controls, including working in a livestock farm, species of livestock, its approximate number and circumstances of contact. For each disease outcome, and each type of livestock, odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated using un...
Immunohistochemical and immunopathologic characterization of superficial stromal immune-mediated keratitis in horses. To describe the immunopathologic characteristics of superficial stromal immune-mediated keratitis (IMMK) immunopathologically by characterizing cellular infiltrate in affected corneas of horses. Methods: 10 client-owned horses with IMMK. Methods: Immunohistochemical staining was performed on keratectomy samples with equine antibodies against the T-cell marker CD3 and B-cell marker CD79a (10 eyes) and the T-helper cytotoxic marker CD4 and T-cell cytotoxic marker CD8 (6 eyes). Percentage of positively stained cells was scored on a scale from 0 (no cells stained) to 4 (> 75% of cells stained)....
Immunoglobulin genes and diversity: what we have learned from domestic animals. This review focuses on the diversity of immunoglobulin (Ig) genes and Ig isotypes that are expressed in domestic animals. Four livestock species-cattle, sheep, pigs, and horses-express a full range of Ig heavy chains (IgHs), including μ, δ, γ, ϵ, and α. Two poultry species (chickens and ducks) express three IgH isotypes, μ, υ, and α, but not δ. The κ and λ light chains are both utilized in the four livestock species, but only the λ chain is expressed in poultry. V(D)J recombination, somatic hypermutation (SHM), and gene conversion (GC) are three distinct mechanisms by which immunog...
Fell Pony syndrome: characterization of developmental hematopoiesis failure and associated gene expression profiles. 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 o...
Expression of essential B cell development genes in horses with common variable immunodeficiency. 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 ...
Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IgE on subpopulations of IgM+ and IgG1+ B-cells in horses. CD23, also called FcεRII, is the low-affinity receptor for IgE and has first been described as a major receptor regulating IgE responses. In addition, CD23 also binds to CD21, integrins and MHC class II molecules and thus has a much wider functional role in immune regulation ranging from involvement in antigen-presentation to multiple cytokine-like functions of soluble CD23. The role of CD23 during immune responses of the horse is less well understood. Here, we expressed equine CD23 in mammalian cells using a novel IL-4 expression system. Expression resulted in high yield of recombinant IL-4/...
Virus-specific CD8⁺ T-cells detected in PBMC from horses vaccinated against African horse sickness virus. African horsesickness (AHS) is an infectious but noncontagious viral disease affecting all species of Equidae. The recall immune response of AHSV naïve horses immunised with an attenuated African horsesickness virus serotype 4 (AHSV4) was characterised using immune assays including ELISPOT, real-time PCR (qPCR) and flow cytometry. The recall immune response detected in PBMC isolated from three inoculated horses showed an upregulation of circulating B lymphocytes that correlated with elevated IL-4 mRNA expression indicative of humoral immunity, but reduced frequency of CD4⁺ cells. In additio...
A case of Borrelia-associated cutaneous pseudolymphoma in a horse. This case report describes a 10-year-old horse that developed multiple dermal papules over the right masseter area following removal of a tick from the same site 3 months earlier. Histological examination of a biopsy from a papule was suggestive of either a T-cell-rich B-cell lymphoma or cutaneous lymphoid hyperplasia, a form of pseudolymphoma sometimes associated with a tick bite. Positive serological testing and PCR of the biopsy sample for Borrelia in conjunction with immunohistochemical testing of the skin biopsy, the clinical history and response to treatment with doxycycline strongly sup...
Mapping B-cell epitopes in equine rhinitis B viruses and identification of a neutralising site in the VP1 C-terminus. Erbovirus is a genus of the family Picornaviridae and equine rhinitis B virus (ERBV) is the sole species. Erboviruses infect horses causing acute respiratory disease and sub-clinical and persistent infections. Despite the high seroprevalence and worldwide distribution of these viruses, the pathogenesis and antigenic structure of the three ERBV serotypes (ERBV1, 2 and 3) is poorly understood. To characterise linear epitopes on ERBV structural proteins, a set of fusion proteins were expressed in Escherichia coli. These proteins were tested in Western blot and ELISA and reactive proteins were als...
Pulmonary angiocentric lymphoma (lymphomatoid granulomatosis) in a donkey. A 36-year-old donkey developed dyspnoea, pyrexia, hypoalbuminaemia and oedema. Following continued clinical deterioration the donkey was humanely destroyed. Grossly, there were numerous nodules (5-10mm) scattered throughout the lung. Microscopically, the lung was infiltrated by an angiocentric and bronchocentric to diffuse mixed population of small mature and atypical lymphocytes, histiocytes, plasma cells and fewer eosinophils. The infiltrate was composed of numerous small mature and fewer atypical CD3(+) T lymphocytes. Low numbers of CD20(+) and CD79a(+) B cells, some atypical, accompanied t...
Presence of mononuclear cells in normal and affected laminae from the black walnut extract model of laminitis. There is increasing evidence of involvement of inflammatory cells in acute laminitis. Objective: To immunolocalise monocytes/macrophages and B and T lymphocytes in the laminar tissue of normal horses and those with black walnut extract (BWE)-induced laminitis. Methods: Immunohistochemistry was used in archived laminar tissue samples from 20 horses divided equally into 4 groups: control animals (CON), and those administered BWE at 1.5 h (1.5H DTP group), at the onset of leucopenia (3H DTP group) and at the onset of lameness (LAM group). Antibodies against CD3, CD20 and CD163 were used to recogn...
Cutaneous T-cell-rich B-cell lymphoma in a horse. Cutaneous malignant lymphomas are rare in horses and comprise predominantly T-cell-rich B-cell lymphomas. They are characterized by multiple tumour nodules affecting predominantly female horses with a survival rate of months to years. At the final stage, metastases to regional lymph nodes occur, whereas widespread organ involvement is rarely reported. In this case report, a cutaneous T-cell-rich B-cell lymphoma in a 7-year-old standardbred gelding with metastases is described. Clinically, multiple cutaneous and subcutaneous nodules, enlarged superficial lymph nodes, rapid weight loss, and vent...
Equine herpesvirus-1 infected peripheral blood mononuclear cell subpopulations during viremia. Infection with equine herpesvirus-1 (EHV-1) causes respiratory disease, late term abortions and equine herpesvirus myeloencephalitis (EHM) and remains an important problem in horses worldwide. Despite increasing outbreaks of EHM in recent years, our understanding of EHM pathogenesis is still limited except for the knowledge that a cell-associated viremia in peripheral blood mononuclear cells (PBMCs) is a critical link between primary respiratory EHV-1 infection and secondary complications such as late-term abortion or EHM. To address this question our objective was to identify which PBMC subpo...