The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice
Details
Publication Year 2014, Volume 7, Issue #338, Page ra77
Journal Title
Sci Signal
Publication Type
Journal Article
Abstract
Maintenance of an appropriate number of plasma cells, long-lived antibody-producing cells that are derived from B cells, is essential for maintaining immunological memory while limiting disease. Plasma cell survival relies on extrinsic factors, the limited availability of which determines the size of the plasma cell population. Mice deficient in the nonreceptor tyrosine kinase Lyn are prone to an autoimmune disease that is characterized by inflammation and an excess of plasma cells (plasmacytosis). We demonstrated that the plasmacytosis was intrinsic to B cells and independent of inflammation. We also showed that Lyn attenuated signaling by signal transducer and activator of transcription 3 (STAT3) and STAT5 in response to the cytokines interleukin-6 (IL-6) and IL-3, respectively, in two previously uncharacterized plasma cell signaling pathways. Thus, in the absence of Lyn, the survival of plasma cells was improved, which enabled the plasma cells to become established in excess numbers in niches in vivo. These data identify Lyn as a key regulator of survival signaling in plasma cells, limiting plasma cell accumulation and autoimmune disease susceptibility.
Publisher
AAAS
WEHI Research Division(s)
Immunology; Cell Signalling And Cell Death; Molecular Medicine
NHMRC Grants
NHMRC/575500 NHMRC/1008288 NHMRC/1025239
Rights Notice
Copyright © 2014 American Association for the Advancement of Science. All Rights Reserved.


Creation Date: 2014-09-12 02:01:41
Last Modified: 2015-09-04 11:43:27
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