Antibody repertoire diversification through VH gene replacement in mice cloned from an IgA plasma cell

Significance Antibodies produced by B cells provide a protective barrier to our organism against the penetration and dissemination of microorganisms. Each antibody recognizes a specific antigen through variable (V) region domains of pairs of immunoglobulin (Ig) heavy (H) and light (L) chains. In mammals, VDJ recombination generates a highly diversified preimmune pool of V H and V L domains. Acquisition of a functional V H rearrangement is thought to prevent further VDJ recombination at the IgH locus. Instead, mice cloned from a terminally differentiated B cell unravel the ability of VDJ recombination to revise a functionally rearranged V H gene through VH replacement. We show that up to 20% of the antibody V gene repertoire of mature B-lymphocytes can be generated through VH replacement.