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The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice


Infantino, S and Jones, SA and Walker, JA and Maxwell, MJ and Light, A and O'Donnell, K and Tsantikos, E and Peperzak, V and Phesse, T and Ernst, M and Mackay, F and Hibbs, ML and Fairfax, KA and Tarlinton, DM, The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice, Science Signaling, 7, (338) Article ra77. ISSN 1945-0877 (2014) [Refereed Article]

DOI: doi:10.1126/scisignal.2005105


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.

Item Details

Item Type:Refereed Article
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Cell development, proliferation and death
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Fairfax, KA (Dr Kirsten Fairfax)
ID Code:134782
Year Published:2014
Web of Science® Times Cited:13
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-09-04
Last Modified:2019-09-04

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