Researchers discovered that bits and pieces of immunoglobulin genes can rearrange themselves in myriad permutations to potentially generate 4 million different antibody proteins. B cells that produce the antibodies that best target invading pathogens are selected for replication. In a sense, these B cells clone themselves. The generation of mutations results in additional antibody diversity and serves to refine this clonal selection over time, Wabl, Steinberg and most other geneticists who study immunology now believe.
In the mouse study reported in Science, Cascalho, assisted by research associate Jamie Wong, compared mutation rates in immunoglobulin genes in B cells and other cells containing zero, one or two copies of normal Pms2 genes. She determined that immunoglobulin genes were mutated at a much higher rate in mice with B cells containing Pms2 compared to mice lacking the gene, suggesting that Pms2 somehow acts differently to play an active role in hypermutation of these genes in B cells.
Prior to cell division, when a cell duplicates its genetic material, the double-stranded DNA helix unzips and each strand serves as a template for making new DNA. Sometimes the template is misread and the wrong building block is inserted into the new strand. DNA-repair enzymes then step in to repair the damage before it becomes fixed.
When DNA-repair enzymes detect a mismatch, they use several clues
to distinguish the old, correct DNA strand from the new, incorrect DNA
strand, so that the mismatch is re
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