3BP2 Deficiency Impairs the Response of B Cells, but Not T Cells, to Antigen Receptor Ligation

Abstract

The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav, and phospholipase C-γ (PLC-γ); and is thought to be important for interleukin-2 gene transcription in T cells. To define the role of 3BP2 in lymphocyte development and function, we generated 3BP2-deficient mice. T-cell development, proliferation, cytokine secretion, and signaling in response to T-cell receptor (TCR) ligation were all normal in 3BP2^−/− mice. 3BP2^−/− mice had increased accumulation of pre-B cells in the bone marrow and a block in the progression of transitional B cells in the spleen from the T1 to the T2 stage, but normal numbers of mature B cells. B-cell proliferation, cell cycle progression, PLC-γ2 phosphorylation, calcium mobilization, NF-ATp dephosphorylation, and Erk and Jnk activation in response to B-cell receptor (BCR) ligation were all impaired. These results suggest that 3BP2 is important for BCR, but not for TCR signaling.

We thank Tatyana Sannikova for excellent technical assistance. We thank John P. Manis for helpful discussions and advice and Hans C. Oettgen for critical review of the manuscript.

This work is supported by USPHS grant 35714.