A Short Domain within Bcl-3 Is Responsible for Its Lymphocyte Survival Activity

• Published in: Annals of the New York Academy of Sciences Vol. 975; no. 1; pp. 132 - 147
• Main Authors: MITCHELL, THOMAS C., THOMPSON, BRUCE S., TRENT, JOHN O., CASELLA, CAROLYN R.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2002
• Subjects: Animals; Ankyrin Repeat; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Bcl-3; Cell Survival; Flow Cytometry - methods; Gene Expression; Gene Transfer Techniques; lymphocyte survival activity; Mice; Models, Molecular; Protein Structure, Tertiary; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - immunology; Sequence Deletion; T-Lymphocytes - cytology; T-Lymphocytes - immunology; Transcription Factors
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2002.tb05947.x

: The NFκB factor Bcl‐3 influences the survival of T cells when they are activated to take part in immune responses. Because treatment of mice with adjuvant results in the increased expression of Bcl‐3 in T cells, where it has survival‐promoting effects, Bcl‐3 may be an important, limiting factor that is supplied to T cells only when they are contributing to an appropriate immune response to infection, and not when spuriously activated by self‐antigens. Although Bcl‐3 is a member of the NFκB/Rel/IκB family of transcription factors, the means by which it promotes T cell survival is not obvious because Bcl‐3 is unique in having an ankyrin repeat domain, like inhibitory IκB proteins, while also possessing domains capable of transcriptional activation, like Rel proteins. In order to understand the basis for the survival activity of Bcl‐3, deletion mutants were engineered and tested in a retroviral gene transfer sytem. We report that most of Bcl‐3 can be deleted without diminishing its ability to prolong the survival of activated T and B cells, and find that its lymphocyte survival domain maps to the vicinity of its first and second ankryin repeats. This information sets the stage for experiments in which a focused search can be made for mediators of Bcl‐3 survival effects.