{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:31:29Z","timestamp":1781105489573,"version":"3.54.1"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,7,3]]},"abstract":"<jats:p>\n                    High affinity antibodies are generated in mice and humans by means of somatic hypermutation (SHM) of variable (V) regions of Ig genes. Mutations with rates of 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    \u201310\n                    <jats:sup>\u22123<\/jats:sup>\n                    per base pair per generation, about 10\n                    <jats:sup>6<\/jats:sup>\n                    -fold above normal, are targeted primarily at V-region hot spots by unknown mechanisms. We have measured mRNA expression of DNA polymerases \u03b9, \u03b7, and \u03b6 by using cultured Burkitt's lymphoma (BL)2 cells. These cells exhibit 5\u201310-fold increases in heavy-chain V-region mutations targeted only predominantly to RGYW (R = A or G, Y = C or T, W = T or A) hot spots if costimulated with T cells and IgM crosslinking, the presumed\n                    <jats:italic>in vivo<\/jats:italic>\n                    requirements for SHM. An \u223c4-fold increase pol \u03b9 mRNA occurs within 12 h when cocultured with T cells and surface IgM crosslinking. Induction of pols \u03b7 and \u03b6 occur with T cells, IgM crosslinking, or both stimuli. The fidelity of pol \u03b9 was measured at RGYW hot- and non-hot-spot sequences situated at nicks, gaps, and double-strand breaks. Pol \u03b9 formed T\u22c5G mispairs at a frequency of 10\n                    <jats:sup>\u22122<\/jats:sup>\n                    , consistent with SHM-generated C to T transitions, with a 3-fold increased error rate in hot- vs. non-hot-spot sequences for the single-nucleotide overhang. The T cell and IgM crosslinking-dependent induction of pol \u03b9 at 12 h may indicate an SHM \u201ctriggering\u201d event has occurred. However, pols \u03b9, \u03b7, and \u03b6 are present under all conditions, suggesting that their presence is not sufficient to generate mutations because both T cell and IgM stimuli are required for SHM induction.\n                  <\/jats:p>","DOI":"10.1073\/pnas.141222198","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"7976-7981","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation"],"prefix":"10.1073","volume":"98","author":[{"given":"Vladimir","family":"Poltoratsky","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461; and Departments of Biological Sciences and Chemistry, University of Southern California, Los Angeles, CA 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