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Immunoglobulin (IG:) genes are hypermutated in mature B cells after interaction with antigen and T cells in a germinal center reaction. We and others have recently shown that the human BCL6 gene is also hypermutated in human peripheral blood memory B cells and tonsils. A preliminary analysis of other non-Ig genes (c-MYC:, S14 and AFP) suggested that they were not mutated in memory B cells. We have now performed an in-depth analysis of three non-Ig genes that are expressed in germinal center B cells in two human donors in whom BCL6 is highly mutated. It was found that the TATA binding protein (TBP), c-MYC: and survivin genes are not hypermutated. This lack of targeting by the Ig hypermutation mechanism must be due to the lack of regulatory DNA elements, since the primary sequences of the three tested genes have at least as high intrinsic mutability indices as the BCL6 gene.

The TATA binding protein, c-Myc and survivin genes are not somatically hypermutated, while Ig and BCL6 genes are hypermutated in human memory B cells