title: 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.
authors.affiliation: Equine Immunology Lab, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. rlt8@cornell.edu
authors.forename: R L
authors.initials: RL
authors.lastname: Tallmadge
authors.forename: K A
authors.initials: KA
authors.lastname: Such
authors.forename: K C
authors.initials: KC
authors.lastname: Miller
authors.forename: M B
authors.initials: MB
authors.lastname: Matychak
authors.forename: M J B
authors.initials: MJ
authors.lastname: Felippe
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics* / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000235:genetics* / Q000276:immunology / Q000662:veterinary*; D006736:Horses; D007150:Immunohistochemistry; D051757:PAX5 Transcription Factor / Q000235:genetics; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051757:PAX5 Transcription Factor