Abstract

The stimulation of a beta-cell by its cognate antigen triggers a series of proliferation and differentiation steps in the development of an antibody- secreting plasma cell. At the molecular level, two key processes can alter the functional antibody gene that encodes the beta-cell antibody heavy chain. Heavy chain genes can both undergo class switching and somatic hypermutation. We have found that a microinjected gamma heavy chain gene can also undergo isotype switching and somatic mutation in transgenic mice. We will analyze transgenic mice to determine the mechanisms that are involved in transgene isotype switching and the nucleotide sequences that are important in allowing the switching process. We will also analyze the cis-acting sequences that are important in directing the hypermutational mechanism to a heavy chain transgene and whether RNA transcription plays a role in the hypermutation process.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI024465-04
Application #
3137477
Study Section
Immunobiology Study Section (IMB)
Project Start
1987-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111

  Publications

Han, Jin-Hwan; Umiker, Benjamin R; Kazimirova, Anastasia A et al. (2014) Expression of an anti-RNA autoantibody in a mouse model of SLE increases neutrophil and monocyte numbers as well as IFN-I expression. Eur J Immunol 44:215-26
Balter, Barbara B; Ciccone, David N; Oettinger, Marjorie A et al. (2012) Mice lacking Sýý tandem repeats maintain RNA polymerase patterns but exhibit histone modification pattern shifts linked to class switch site locations. Mol Immunol 52:1-8
Shansab, Maryam; Eccleston, Jennifer M; Selsing, Erik (2011) Translocation of an antibody transgene requires AID and occurs by interchromosomal switching to all switch regions except the mu switch region. Eur J Immunol 41:1456-64
Shansab, Maryam; Selsing, Erik (2011) p21 is dispensable for AID-mediated class switch recombination and mutagenesis of immunoglobulin genes during somatic hypermutation. Mol Immunol 48:973-8
Eccleston, Jennifer; Yan, Catherine; Yuan, Karen et al. (2011) Mismatch repair proteins MSH2, MLH1, and EXO1 are important for class-switch recombination events occurring in B cells that lack nonhomologous end joining. J Immunol 186:2336-43
Eccleston, Jennifer; Schrader, Carol E; Yuan, Karen et al. (2009) Class switch recombination efficiency and junction microhomology patterns in Msh2-, Mlh1-, and Exo1-deficient mice depend on the presence of mu switch region tandem repeats. J Immunol 183:1222-8
Han, Jin-Hwan; Akira, Shizuo; Calame, Kathryn et al. (2007) Class switch recombination and somatic hypermutation in early mouse B cells are mediated by B cell and Toll-like receptors. Immunity 27:64-75
Wuerffel, Robert; Wang, Lili; Grigera, Fernando et al. (2007) S-S synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase. Immunity 27:711-22
Selsing, Erik (2006) Ig class switching: targeting the recombinational mechanism. Curr Opin Immunol 18:249-54
Min, Irene M; Rothlein, Lisa R; Schrader, Carol E et al. (2005) Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2. J Exp Med 201:1885-90

Showing the most recent 10 out of 22 publications