Gene Expression Profiles of CD21low B cells in Common Variable Immunodeficiency

The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. Since these circulating atypical B cells in the blood of CVID patients could not be assigned to any certain B cell differentiation stage in the periphery, they were designated as CD21low B cells. Although, CD21low B cells are polyclonal and unmutated IgM+IgD+ B cells like naive B cells in the peripheral blood, they reveal several distinct phenotypic and functional features. In order to uncover the the global programme of gene expression underlying these differences and changes in CD21low B cells we have performed microarray hybridization experiments and identified differentially expressed genes which define a distinct gene expression profile in CD21low B cells compared to naive B cells. Leucocytes were separated by Ficoll gradient from peripheral blood of healthy donors (HD) and CVID patients. CD19+CD27-CD38+CD21+ naive B cells of HD as well as naive and CD19hiCD27-CD38lowCD21low (CD21low) B cells of CVID patients were sorted using a MoFlow cell sorter. RNA was extracted from sorted ex vivo B cell subpopulations and hybridized on Affymetrix microarrays. Gene expression profiles were compared between CD21low B cells and naive B cells of CVID patients as well as HD naive B cells.