International Immunology Advance Access originally published online on September 7, 2009
International Immunology 2009 21(11):1225-1237; doi:10.1093/intimm/dxp090
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Enhanced B cell activation in the absence of CD81
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Correspondence to: S. Levy; E-mail: slevy{at}stanford.edu
CD81 is a component of the CD19/CD21 co-receptor complex in B cells. However, the role of CD81 in B cell activation has not been clearly elucidated. Here, we demonstrate that Cd81–/– B cells stimulated via their B cell receptor fluxed higher intracellular-free calcium ion along with increased phosphorylation of spleen tyrosine kinase and phospholipase gamma 2. Additionally, Cd81–/– B cells responded to toll like receptor 4 stimulation with increased nuclear factor-kappa B activation, cell proliferation and antibody secretion compared with wild-type B cells. Cd81–/– mice also mounted a significantly higher immune response to T-independent antigens than their wild-type counterparts. Finally, analysis of Cd81–/– B cells that were generated by bone marrow transplantation into Rag1–/– mice confirmed that the hyperactive phenotype is not dependent on the CD81-deficient environment. Taken together, these results indicate that CD81 plays a negative role in B cell activation in vitro and in vivo.
Keywords: B cell activation, calcium mobilization, knockout, signal transduction, tetraspanin, TLR4
Transmitting editor: P. W. Kincade
Received 16 January 2009, accepted 6 August 2009.