Inducible CO-stimulator molecule, a candidate gene for defective isotype switching, is normal in patients with hyper-IgM syndrome of unknown molecular diagnosis.

Background: Inducible CO-stimulatory molecule (ICOS), the third member of the CD28/CTLA4 family, is expressed by activated T cells and interacts with its ligand (ICOSL, B7-related protein-1 [B7RP-1]) that is constitutively expressed by B cells. The interaction of ICOS with its ligand leads to terminal differentiation of B cells to plasma cells. ICOS-deficient mice fail to undergo immunoglobulin-class switch recombination (CSR) and germinal center formation, suggesting that ICOS could be a candidate gene for phenotypic hyper-IgM (HIGM) syndromes characterized by recurrent infections, low serum IgG and IgA, and normal or elevated IgM.