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The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice
journal contribution
posted on 2023-05-20, 06:53 authored by Infantino, S, Jones, SA, Walker, JA, Maxwell, MJ, Light, A, O'Donnell, K, Tsantikos, E, Peperzak, V, Phesse, T, Ernst, M, Mackay, F, Hibbs, ML, Kirsten FairfaxKirsten Fairfax, Tarlinton, DMMaintenance 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.
History
Publication title
Science SignalingVolume
7Issue
338Article number
ra77Number
ra77ISSN
1945-0877Department/School
Menzies Institute for Medical ResearchPublisher
American Association for the Advancement of SciencePlace of publication
United StatesRepository Status
- Restricted