Enhanced B cell activation in the absence of CD81.
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.
Sanyal
Mrinmoy
M
Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Fernandez
Rosemary
R
Levy
Shoshana
S
D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000955:Antigens, T-Independent / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000276:immunology / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D060225:Tetraspanin 28; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism
D015703:Antigens, CD; D000955:Antigens, T-Independent; C554799:Cd81 protein, mouse; D018398:Homeodomain Proteins; D016328:NF-kappa B; D060225:Tetraspanin 28; D051197:Toll-Like Receptor 4; C064658:RAG-1 protein; D011505:Protein-Tyrosine Kinases; D002118:Calcium