Seeing i-to-I

Blood cells display diverse antigen molecules on their surface, including chains of N-acetyllactosamine carbohydrates. These can manifest in a linear ‘i’ form or branched ‘I’ form; the i variant is most prevalent during early development in human red blood cells, but by the age of 18 months these cells predominantly display the I antigen.

Previous research from Lung-Chih Yu of the National Taiwan University has highlighted a key role for the transcriptional regulator C/EBPα in regulating genes that facilitate this i-to-I transition in red blood cells. However, C/EBPα also contributes to development of white blood cells known as granulocytes, and Yu and co-workers have now determined that these cells employ a similar mechanism for I antigen production¹.

C/EBPα activity is modulated by the addition of phosphate molecules to specific amino acids, and the researchers identified a single phosphorylation site at serine-21 that appears to act as a direct switch for triggering I antigen expression. Working with cells that can differentiate into either red blood cells or granulocytes, they demonstrated that I production is directly correlated with removal of phosphorylation from this C/EBPα residue in blood cells from both lineages, suggesting that this may represent a common pathway for driving this antigenic transition in diverse cell types.