Li, X, Gadzinsky, A, Gong, L et al. (9 more authors) (2018) Cbl Ubiquitin Ligases Control B Cell Exit from the Germinal-Center Reaction. Immunity, 48 (3). 530-541.e6. ISSN 1074-7613
Abstract
Selective expansion of high-affinity antigen-specific B cells in germinal centers (GCs) is a key event in antibody affinity maturation. GC B cells with improved affinity can either continue affinity-driven selection or exit the GC to differentiate into plasma cells (PCs) or memory B cells. Here we found that deleting E3 ubiquitin ligases Cbl and Cbl-b (Cbls) in GC B cells resulted in the early exit of high-affinity antigen-specific B cells from the GC reaction and thus impaired clonal expansion. Cbls were highly expressed in GC light zone (LZ) B cells, where they promoted the ubiquitination and degradation of Irf4, a transcription factor facilitating PC fate choice. Strong CD40 and BCR stimulation triggered the Cbl degradation, resulting in increased Irf4 expression and exit from GC affinity selection. Thus, a regulatory cascade that is centered on the Cbl ubiquitin ligases ensures affinity-driven clonal expansion by connecting BCR affinity signals with differentiation programs.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) 2018, Elsevier Inc. This is an author produced version of a paper published in Immunity. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Germinal center; B cell; Cbl ubiquitin ligase; antibody affinity maturation; Irf4 |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Haematology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Nov 2018 17:21 |
Last Modified: | 20 Mar 2019 01:39 |
Status: | Published |
Publisher: | Elsevier (Cell Press) |
Identification Number: | 10.1016/j.immuni.2018.03.006 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:138174 |