Bone marrow gene expression in healthy control horses and equine CVID patients

Common Variable ImmunoDeficiency (CVID) in horses is characterized by a late-onset depletion of B lymphocytes, decreased serum IgM and IgG concentrations, and recurrent bacterial infections. The phenotype of equine CVID is similar to that of CVID-affected humans who lack B lymphocytes. We have determined that the loss of B lymphocytes is due to a failure of differentiation in the bone marrow of equine CVID patients. Transcriptome sequencing was undertaken to assess the expression of genes and transcription factors known to be essential for B cell differentiation, and simultaneously obtain a comprehensive view of gene expression in the bone marrow. Analysis of bone marrow mRNA expression from CVID horses revealed a significant decrease in E2A (p < 0.05) and a marked decrease in PAX5 (p < 0.01) expression in comparison to healthy horses. E2A and PAX5 are transcription factors essential to successful B cell differentiation, and are indicative of specific B cell stages. This data demonstrates that the block in B cell hematopoiesis in the bone marrow of equine CVID patients occurs at the transition from pre-pro B cells to pro-B cells.