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Requirements for follicular exclusion and competitive elimination of autoantigen-binding B cells

Item Type:Article
Title:Requirements for follicular exclusion and competitive elimination of autoantigen-binding B cells
Creators Name:Ekland, E.H. and Forster, R. and Lipp, M. and Cyster, J.G.
Abstract:Results from several mouse tolerance models indicate that autoreactive B cells in peripheral lymphoid organs develop an anergic phenotype, migrate to the boundary between the T cell zone and the B cell follicle (T/B boundary), and undergo rapid cell death. We have used B cells from mice that are double-transgenic for soluble hen egg lysozyme (HEL) and an Ig that recognizes HEL with a high affinity to characterize the mechanisms underlying the migration and elimination of autoreactive B cells. In contrast to the situation for acutely activated B cells, we find that anergic B cells have reduced levels of CXCR5, the receptor for the follicular chemokine, CXCL13, and this contributes to their exclusion from follicles. CCR7 expression is required for follicular exclusion of anergic cells, although up-regulation of the receptor does not appear to be necessary. By TUNEL analysis, we observe that excluded anergic cells die in situ at the T/B boundary. We also show that this elimination occurs via a Fas-independent mechanism. Using CCR7 -/-Ig HEL-transgenic B cells we find that localization to the T/B boundary is not a necessary event to achieve the competitive elimination of autoantigen-binding B cells. These findings characterize the mechanism for follicular exclusion of autoantigen-binding B cells and they indicate that B cells compete for survival by mechanisms that are separate from competition for the follicular niche.
Keywords:Adoptive Transfer, Autoantigens, B-Lymphocyte Subsets, CD95 Antigens, Cell Death, Cell Movement, Chemokine Receptors, Clonal Anergy, Competitive Binding, Cytokine Receptors, Inbred C57BL Mice, Interphase, Knockout Mice, Lymphocyte Activation, Lymphocyte Transfusion, Lymphoid Tissue, T-Lymphocyte Subsets, Transgenic Mice, Animals, Mice
Source:Journal of Immunology
ISSN:0022-1767
Publisher:American Association of Immunologists (U.S.A.)
Volume:172
Number:8
Page Range:4700-4708
Date:15 April 2004
Official Publication:https://doi.org/10.4049/jimmunol.172.8.4700
PubMed:View item in PubMed

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