Terminal defects of B lymphocyte differentiation.

In humans several abnormalities can occur during terminal B cell differentiation, leading to primary humoral immunodeficiencies. A recent study provided evidence of a qualitative defect of the affinity antibody maturation in some patients affected with common variable immunodeficiency syndrome, the molecular basis of which remains unknown. Several genetic defects in class switch recombination leading to a hyper-IgM syndrome have recently been delineated. Besides the well-known role of CD40-CD40 ligand interaction, they definitively demonstrate the requirement of CD40-mediated nuclear factor kappa B activation and the essential role of a newly described molecule, the activation-induced cytidine deaminase, in B cell terminal differentiation.