SOCS3 Deletion in B Cells Alters Cytokine Responses and Germinal Center Output
- Author(s)
- Jones, SA; White, CA; Robb, L; Alexander, WS; Tarlinton, DM;
- Details
- Publication Year 2011-12-15,Volume 187,Issue #12,Page 6318-6326
- Journal Title
- JOURNAL OF IMMUNOLOGY
- Publication Type
- Journal Article
- Abstract
- B cell behavior is fine-tuned by internal regulatory mechanisms and external cues such as cytokines and chemokines. Suppressor of cytokine signaling 3 (SOCS3) is a key regulator of STAT3-dependent cytokine responses in many cell types and has been reported to inhibit CXCL12-induced retention of immature B cells in the bone marrow. Using mice with SOCS3 exclusively deleted in the B cell lineage (Socs3(Delta/Delta)mb1cre(+)), we analyzed the role of SOCS3 in the response of these cells to CXCL12 and the STAT3-inducing cytokines IL-6 and IL-21. Our findings refute a B cell-intrinsic role for SOCS3 in B cell development, because SOCS3 deletion in the B lineage did not affect B cell populations in naive mice. SOCS3 was strongly induced in B cells stimulated with IL-21 and in plasma cells exposed to IL-6. Its deletion permitted excessive and prolonged STAT3 signaling following IL-6 stimulation of plasma cells and, in a T cell-dependent immunization model, reduced the number of germinal center B cells formed and altered the production of Ag-specific IgM and IgE. These data demonstrate a novel regulatory signal transduction circuit in plasma cells, providing, to our knowledge, the first evidence of how these long-lived, sessile cells respond to the external signals that mediate their longevity. The Journal of Immunology, 2011, 187: 6318-6326.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Keywords
- FOLLICULAR-HELPER-CELLS; TRANSGENIC MICE; STAT3; IL-21; DIFFERENTIATION; GENERATION; IGE; INTERLEUKIN-6; EXPRESSION; MEMORY
- Research Division(s)
- Immunology; Cancer And Haematology
- Publisher's Version
- https://doi.org/10.4049/jimmunol.1102057
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3254674/- Terms of Use/Rights Notice
- Copyright © 2011 by The American Association of Immunologists, Inc.
Creation Date: 2011-12-15 12:00:00