PMID: 2499654Jun 1, 1989Paper

Early onset of somatic mutation in immunoglobulin VH genes during the primary immune response

The Journal of Experimental Medicine
N S LevyPatricia J Gearhart

Abstract

The dynamics of somatic mutation in Ig variable genes was investigated in order to define a population of B cells undergoing mutation. BALB/cJ mice were injected with PC-KLH, and splenic RNA was prepared 5, 7, and 13 d later. The mRNA was annealed to gamma constant region primers to make cDNA transcripts encoding VH genes. 103 cDNA clones corresponding to 18 different genes from the VH7183, VH3660, and VHS107 subfamilies were sequenced to identify mutation. VH genes had a low level of mutation on day 5 after immunization and accumulated more mutation by day 7 at a rate of 10(-3) mutations per nucleotide per generation. However, by day 13, the number of mutations per gene did not increase, and most of the substitutions encoded replacement amino acid changes that were clustered in the hypervariable regions, indicating that the mutational process was less active during the second week and that antigen selection had occurred. The data are consistent with a developmentally regulated mechanism in which mutation is activated during the first week of the primary immune response for a limited time period, after which selection acts to preserve the beneficial mutants.

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Citations

Mar 1, 1991·Research in Immunology·V K Tsiagbe, G J Thorbecke
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·D W Bahler, R Levy
Aug 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A H LiuL J Wysocki
Jan 18, 1994·Proceedings of the National Academy of Sciences of the United States of America·C DemaisonM Zouali
Feb 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·J Foote, H N Eisen
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·M ZhuM D Scharff
Jul 1, 1991·The Journal of Cell Biology·P A SchweitzerL D Shultz
Jul 1, 1993·The Journal of Experimental Medicine·M G McHeyzer-WilliamsG J Nossal
Apr 1, 1995·The Journal of Experimental Medicine·C MillerJ Cerny
Jul 11, 1990·Nucleic Acids Research·H L GovanJ Braun
Feb 24, 2001·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·B Tippin, M F Goodman
Nov 1, 1994·Scandinavian Journal of Immunology·E KällbergT Leanderson
Apr 1, 1992·Immunological Reviews·V K TsiagbeG J Thorbecke
Feb 26, 1998·Immunological Reviews·H SongJ Cerny
May 29, 1998·Immunological Reviews·U StorbT E Martin
Apr 1, 1992·The Journal of Clinical Investigation·C HuangB D Stollar
Dec 29, 2004·Journal of Clinical Immunology·Reng-Rong DaYufen Qin
Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·N S GreenM D Scharff
Dec 1, 1992·Leukemia & Lymphoma·J M Johnston, W L Carroll
Jan 1, 1991·Leukemia & Lymphoma·T J KippsD A Carson
Jul 15, 2005·Annals of the New York Academy of Sciences·Zhenming XuPaolo Casali
Jan 1, 1992·Current Biology : CB·J L RabinowitzM D Scharff

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