Self-reactive B lymphocytes overexpressing Bcl-x(L) escape negative selection and are tolerized by clonal anergy and receptor editing

Wei Fang, Bennett C. Weintraub, Brenda Dunlap, Paul Garside, Kathryn A Pape, Marc Jenkins, Christopher C. Goodnow, Daniel L Mueller, Timothy W. Behrens

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

Self-reactive B cells Tg for both a bcl-x(L) death inhibitory gene and an Ig receptor recognizing hen egg lysozyme (HEL-Ig) efficiently escaped developmental arrest and deletion in mice expressing membrane-bound self- antigen (mHEL). In response to the same antigen, Tg HEL-Ig B cells not expressing bcl-x(L) were deleted, while cells expressing bcl-2 were arrested at the immature B stage. Bcl-x(L) Tg B cells escaping negative selection were anergic in both in vitro and in vivo assays and showed some evidence for receptor editing. These studies suggest that Bcl-x may have a distinct role in controlling survival at the immature stage of B cell development and demonstrate that tolerance is preserved when self-reactive B cells escape central deletion.

Original languageEnglish (US)
Pages (from-to)35-45
Number of pages11
JournalImmunity
Volume9
Issue number1
DOIs
StatePublished - Jul 1998

Bibliographical note

Funding Information:
We would like to thank G. Briggs for excellent animal husbandry and technical assistance with genotyping and M. Schlissel for discussions and assistance with primer design. This work was supported by grants from the National Institutes of Health (to M. K. J, D. L. M., and T. W. B.), an American College of Rheumatology/Arthritis Foundation Investigator Award (T. W. B.), and a Leukemia Society of America Scholar Award (T. W. B).

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

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