B cell development in common variable immunodeficiency of horses
Common Variable Immunodeficiency (CVID) has been diagnosed in several horses, and is characterized by a lack of B cells in peripheral blood and lymphoid tissues. CVID manifests in adult horses, causes recurrent bacterial infections, agammagloblulinemia or hypoglobulinemia, and impaired response to vaccination. Serial immunologic testing in peripheral blood reveals persistent, severe B cell lymphopenia in all patients. Immunohistochemical and histopathological analysis of lymphoid tissues of affected CVID horses revealed an absence of B cells in the bone marrow and spleen. Standard RT-PCR of bone marrow revealed that all equine CVID patients expressed E2A and EBF1, which are transcriptional factors that directly regulate B cell differentiation through PAX5 expression. Yet, PAX5, CD19 and IgM gene expression was variable, with some patients missing the expression of those genes in their bone marrow. Quantitative RT-PCR revealed that the expression of both PAX5 and CD19 was significantly reduced in equine CVID patients when compared to healthy horses (p < 0.001). In addition, the PAX5/EBF1 ratio was also significantly reduced in CVID patients (p < 0.02). Altogether, our data suggest that B cell depletion in horses with CVID is caused by impaired B cell development in the bone marrow at the level of pro-B cells.
Senior seminar paperSeminar SF610.1 2010
Horses -- Immunology