Single cell variations in expression of codominant alleles A and B on RBC of AB blood group individuals

One of the key questions in biology is whether all cells of a “cell type” have more or less the same phenotype, especially with relation to non-imprinted autosomal loci. Recent studies point to differential allelic expression of autosomal genes being a prevalent phenomenon responsible to confer phenotypic variability at individual cell level. However, most studies have been carried out in actively transcribing cells. Here we display cellular mosaicism arising from differential allelic expression for the cell surface glycoprotein in the enucleated RBCs. We studied the expression of the A and B histo-blood group antigens encoded by the co-dominant alleles in individual RBCs using immunofluorescence. We assessed the relative levels of the co-dominant alleles I A and I B in 2512 RBC from 24 individuals with AB blood group using Cy3- and FITC- tagged antibodies. Quantification of individual fluorescence intensities from each cell and test of their normal distribution revealed that contrary to the general belief that all RBC in AB individuals express both antigens in comparable amounts, they segregated into 4 groups: showing normal distribution for both antigens, either antigen, and neither antigen; the deviation from normal distribution could not be correlated to maternal/paternal origin, thus appear to be stochastic. Surprisingly, very few people showed any correlation between the amounts of these two antigens on RBC. In fact, the ratio of antigen A to B in the entire set of samples spanned over 5 orders of magnitude. This variability in amount of the antigens A and/or B, combined with a lack of correlation between the amounts of these two antigens resulted in unique staining patterns for RBC, generating widespread mosaicism in the RBC population of AB blood group individuals.