SOMATIC MUTATION OF IMMUNOGLOBULIN-V GENES IN-VITRO

The molecular mechanism behind affinity maturation is the introduction of point mutations in immunoglobulin (Ig) V genes, followed by the se lective proliferation of B cells expressing mutants with increased aff inity for antigen. An in vitro culture system was developed in which s omatic hypermutation of Ig V genes was sustained in primed B cells. Co gnate T cell help and cross-linking of the surface Ig were required, w hereas the addition of lipopolysaccharide or a CD40 ligand to drive pr oliferation was insufficient. This system should facilitate understand ing of the molecular and cellular mechanisms that regulate somatic mut ation and B cell selection.