Enhanced B Cell Activation in the Absence of CD81

CD81 is a component of the CD19/CD21 coreceptor complex in B cells. This tetraspanin molecule was previously shown to enable membrane reorganization in B cells responding to complement-bound antigens. Here we stimulated B cells via their B cell receptor (BCR) and demonstrate that Cd81^−/− B cells fluxed higher intracellular free calcium ion along with increased phosphorylation of PLCγ₂ and Syk. The stimulated Cd81^−/− B cells also proliferated faster and secreted higher amounts of antibodies. Moreover, activation of the TLR4 pathway in Cd81^−/− B cells induced increased proliferation and antibody secretion. Furthermore, Cd81^−/− mice mounted a significantly higher immune response to T-cell independent antigens than their wildtype counterparts. Finally, analysis of Cd81^−/− B cells that were generated by bone marrow transplantation into Rag1^−/− mice confirmed a cell intrinsic hyperactive phenotype. Taken together, these results indicate that CD81 plays a negative role in B cell activation in vitro and in vivo.