Increased IL-12 inhibits B cells' differentiation to germinal center cells and promotes differentiation to short-lived plasmablasts
Open Access
- 22 September 2008
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 205 (10), 2437-2448
- https://doi.org/10.1084/jem.20070731
Abstract
B cells activated by antigen in T cell–dependent immune responses can become short-lived plasma cells, which remain in the spleen, or germinal center–derived memory or plasma cells, which show evidence of affinity maturation and, in the case of plasma cells, migrate to the bone marrow. We show that this cell fate decision can be governed by the cytokine environment engendered by activated dendritic cells (DCs). DCs from mice lacking the Fc receptor γ chain exhibited an activated phenotype in vitro. They secreted more of the proinflammatory cytokine IL-12, which led to the preferential generation of short-lived splenic plasma cells, with ensuing low affinity antibodies and a diminished recall response. Understanding the factors that regulate antigen-activated B cell differentiation and memory cell formation has implications for both antibody-mediated autoimmune disease and protective antibody responses.Keywords
This publication has 42 references indexed in Scilit:
- Affinity of antigen encounter and other early B-cell signals determine B-cell fateCurrent Opinion in Immunology, 2007
- FcγRIII-Dependent Inhibition of Interferon-γ Responses Mediates Suppressive Effects of Intravenous Immune GlobulinImmunity, 2007
- In human B cells, IL-12 triggers a cascade of molecular events similar to Th1 commitmentBlood, 2003
- Blood Dendritic Cells Interact with Splenic Marginal Zone B Cells to Initiate T-Independent Immune ResponsesImmunity, 2002
- CD22 Regulates B Cell Receptor-mediated Signals via Two Domains That Independently Recruit Grb2 and SHP-1Published by Elsevier BV ,2001
- Antigen-Specific B Cell MemoryThe Journal of Experimental Medicine, 2000
- FcR γ chain deletion results in pleiotrophic effector cell defectsCell, 1994
- Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.The Journal of Experimental Medicine, 1992
- Tumor necrosis factor alpha in murine systemic lupus erythematosus disease models: Implications for genetic predisposition and immune regulationCytokine, 1991
- Direct measurement of antibody affinity distribution by Haften-inhibition enzyme immunoassayMolecular Immunology, 1984