3BP2 deficiency impairs the response of B cells, but not T cells, to antigen receptor ligation.
The adapter protein 3BP2 is expressed in lymphocytes; binds to Syk/ZAP-70, Vav, and phospholipase C-gamma (PLC-gamma); 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-gamma2 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.
de la Fuente
Miguel A
MA
Division of Immunology, Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA.
Kumar
Lalit
L
Lu
Bao
B
Geha
Raif S
RS
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D002470:Cell Survival; D018076:DNA, Complementary / Q000235:genetics; D007136:Immunoglobulins / Q000097:blood; D038041:Lymphopoiesis; D051379:Mice; D018345:Mice, Knockout; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; C484644:Sh3bp2 protein, mouse