In vivo assessment of the relative contributions of deletion, anergy, and editing to B cell self-tolerance

Keli L. Hippen, Brian R. Schram, Lina E. Tze, Kathryn A. Pape, Marc K. Jenkins, Timothy W. Behrens

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

In normal B cell development, a large percentage of newly formed cells bear receptors with high levels of self-reactivity that must be tolerized before entry into the mature B cell pool. We followed the fate of self-reactive B cells expressing high affinity anti-hen egg lysozyme (HEL) Ag receptors exposed in vivo to membrane HEL in a setting in which the anti-HEL L chain was "knocked-in" at the endogenous L chain locus. These mice demonstrated extensive and efficient L chain receptor editing responses and had B cell numbers comparable to those found in animals lacking membrane Ag. BrdU labeling indicated that the time required for editing in response to membrane HEL was ∼6 h. In mice transgenic for soluble HEL, anti-HEL B cells capable of editing showed evidence for both editing and anergy. These data identify receptor editing as a major physiologic mechanism by which highly self-reactive B cells are tolerized to membrane and soluble self-Ags.

Original languageEnglish (US)
Pages (from-to)909-916
Number of pages8
JournalJournal of Immunology
Volume175
Issue number2
DOIs
StatePublished - Jul 15 2005

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

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