Regulation of germinal center responses and B-cell memory by the chromatin modifier MOZ
Details
Publication Year 2014-07-01, Volume 111, Issue #26, Page 9585-90
Journal Title
Proceedings of the National Academy of Sciences of the United States of America
Publication Type
Journal Article
Abstract
Memory B cells and long-lived bone marrow-resident plasma cells maintain humoral immunity. Little is known about the intrinsic mechanisms that are essential for forming memory B cells or endowing them with the ability to rapidly differentiate upon reexposure while maintaining the population over time. Histone modifications have been shown to regulate lymphocyte development, but their role in regulating differentiation and maintenance of B-cell subsets during an immune response is unclear. Using stage-specific deletion of monocytic leukemia zinc finger protein (MOZ), a histone acetyltransferase, we demonstrate that mutation of this chromatin modifier alters fate decisions in both primary and secondary responses. In the absence of MOZ, germinal center B cells were significantly impaired in their ability to generate dark zone centroblasts, with a concomitant decrease in both cell-cycle progression and BCL-6 expression. In contrast, there was increased differentiation to IgM and low-affinity IgG1(+) memory B cells. The lack of MOZ affected the functional outcome of humoral immune responses, with an increase in secondary germinal centers and a corresponding decrease in secondary high-affinity antibody-secreting cell formation. Therefore, these data provide strong evidence that manipulating epigenetic modifiers can regulate fate decisions during humoral responses, and thus could be targeted for therapeutic intervention.
Publisher
National Academy of Sciences
WEHI Research Division(s)
Immunology; Bioinformatics; Development And Cancer
NHMRC Grants
NHMRC/1054925 NHMRC/1022458
Rights Notice
Copyright © 2014 National Academy of Sciences


Creation Date: 2014-07-09 09:33:57
Last Modified: 2015-09-07 11:30:53
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