Abstract

The elements controlling expression of antibody genes will be analyzed. These include the DNA sequence at the region of transcription of RNA of expressed kappa chains and of the unrearranged kappa locus. In addition kappa genes that are not transcribed will be analyzed. A comparison of these different types will elucidate the requirements for transcription. Further amino acid sequence analysis of related variable (V) regions such as the V 21 group will be carried out to add to our examples of apparent somatic variation of V region genes. Variant sequences will be compared to germline sequences to determine the exact nature of the variation. Such comparisons should lead to an understanding of the mechanism(s) of diversification. Related V region genes will be compared between inbred strains. The basis of the polymorphism at these groups of genes will be analyzed by comparisons of V region genes and their flanking sequences. Serological and chemical methods for identifying VH groups have been developed. These will be applied to an anaysis of serum and surface antibodies in order to assess the number of VH groups (and in turn VH genes) expressed by inbred mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM020964-13
Application #
3270203
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1977-01-01
Project End
1986-12-31
Budget Start
1986-01-01
Budget End
1986-12-31
Support Year
13
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Institute for Cancer Research
Department
Type
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19111

  Publications

Kalinina, Olga; Wang, Yue; Sia, Kevin et al. (2014) Light chain editors of anti-DNA receptors in human B cells. J Exp Med 211:357-64
Schoettler, Nathan; Ni, Dongyao; Weigert, Martin (2012) B cell receptor light chain repertoires show signs of selection with differences between groups of healthy individuals and SLE patients. Mol Immunol 51:273-82
Meng, Wenzhao; Yunk, Lenka; Wang, Li-San et al. (2011) Selection of individual VH genes occurs at the pro-B to pre-B cell transition. J Immunol 187:1835-44
Kalinina, Olga; Doyle-Cooper, Colleen M; Miksanek, Jennifer et al. (2011) Alternative mechanisms of receptor editing in autoreactive B cells. Proc Natl Acad Sci U S A 108:7125-30
Louzoun, Yoram; Vider, Tal; Weigert, Martin (2006) T-cell epitope repertoire as predicted from human and viral genomes. Mol Immunol 43:559-69
Witsch, Esther J; Cao, Hong; Fukuyama, Hidehiro et al. (2006) Light chain editing generates polyreactive antibodies in chronic graft-versus-host reaction. J Exp Med 203:1761-72
Chen, Ching; Li, Hui; Tian, Qi et al. (2006) Selection of anti-double-stranded DNA B cells in autoimmune MRL-lpr/lpr mice. J Immunol 176:5183-90
Li, Yijin; Louzoun, Yoram; Weigert, Martin (2004) Editing anti-DNA B cells by Vlambdax. J Exp Med 199:337-46
Li, Yijin; Li, Hui; Ni, Dongyao et al. (2002) Anti-DNA B cells in MRL/lpr mice show altered differentiation and editing pattern. J Exp Med 196:1543-52
Detours, V; Mehr, R; Perelson, A S (2000) Deriving quantitative constraints on T cell selection from data on the mature T cell repertoire. J Immunol 164:121-8

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