Receptor revision of immunoglobulin heavy chain variable region genes in normal human B lymphocytes

Contrary to the general precepts of the clonal selection theory, several re cent studies have provided evidence for the secondary rearrangement of immu noglobulin (Ig) genes in peripheral lymphoid tissues. These analyses typica lly used transgenic mouse models and have only detected secondary recombina tion of Ig light chain genes. Although Ig heavy chain variable region (V-H) genes encode a substantial element of antibody combining site specificity, there is scant evidence for V-H gene rearrangement in the periphery, leavi ng the physiological importance of peripheral recombination questionable. T he extensive somatic mutations and clonality of the IgD(+)Strictly-IgM(-)CD 38(+) human tonsillar B cell subpopulation have now allowed detection of th e first clear examples of receptor revision of human V-H genes. The revised VDT genes contain "hybrid" V-H gene segments consisting of portions from t wo separate germline V-H genes, a phenomenon previously only detected due t o the pressures of a transgenic system.