The Journal of Immunology, Vol 157, Issue 1 39-47, Copyright © 1996 by American Association of Immunologists

ARTICLES

Antigen-receptor engagement in B cells induces nuclear expression of STAT5 and STAT6 proteins that bind and transactivate an IFN-gamma activation site

JG Karras, Z Wang, SJ Coniglio, DA Frank and TL Rothstein
Department of Medicine, Boston University Medical Center, MA 02118, USA.

The signal transducer and activator of transcription (STAT) family of transcription factors is triggered by cytokine and growth factor receptors in a number of cell types, and binds to a consensus sequence defined in part by the IFN-gamma activation site (GAS). It is not known whether these transcription factors respond to other kinds of growth stimuli, and, with particular relevance to lymphocytes, it is not known whether STAT proteins participate in Ag-specific responses. To determine the role of STAT proteins, coupling between Ag-receptor cross- linking and nuclear expression of DNA-binding protein complexes that recognize GAS sequences was evaluated. Ag-receptor triggering in primary B lymphocytes stimulated nuclear expression of a complex that specifically binds the IFN response factor-1 (IRF-1) GAS sequence, and is distinguished by electrophoretic mobility and GAS preference from IRF-1 GAS-binding complexes induced by IFN-gamma. Activation of nuclear IRF-1 GAS-binding activity by sIg was inhibited by the tyrosine kinase inhibitor, herbimycin A, and binding activity was eliminated by tyrosine phosphatase treatment. Activation of IRF-1 GAS-binding activity was blocked by depletion of protein kinase C. The IRF-1 GAS- binding activity induced by sIg engagement in B cells was transcriptionally active, and was found to consist of immunoreactive STAT5 and STAT6 proteins. This work demonstrates that the STAT signaling pathway previously associated with cytokine signaling is triggered in B lymphocytes through Ag-receptor engagement in a protein kinase C-dependent fashion. This heretofore described cytokine signaling pathway may play a role in bringing about Ag-specific proliferative and differentiative responses.

This article has been cited by other articles:

				A. L. Wurster, V. L. Rodgers, M. F. White, T. L. Rothstein, and M. J. Grusby Interleukin-4-mediated Protection of Primary B Cells from Apoptosis through Stat6-dependent Up-regulation of Bcl-xL J. Biol. Chem., July 19, 2002; 277(30): 27169 - 27175. [Abstract] [Full Text] [PDF]

				T. J. Schneider, G. M. Fischer, T. J. Donohoe, T. P. Colarusso, and T. L. Rothstein A Novel Gene Coding for a Fas Apoptosis Inhibitory Molecule (FAIM) Isolated from Inducibly Fas-resistant B Lymphocytes J. Exp. Med., March 15, 1999; 189(6): 949 - 956. [Abstract] [Full Text] [PDF]

				M. A. Sherman, V. H. Secor, and M. A. Brown IL-4 Preferentially Activates a Novel STAT6 Isoform in Mast Cells J. Immunol., March 1, 1999; 162(5): 2703 - 2708. [Abstract] [Full Text] [PDF]

				R. Berland and H. H. Wortis An NFAT-Dependent Enhancer Is Necessary for Anti-IgM-Mediated Induction of Murine CD5 Expression in Primary Splenic B Cells J. Immunol., July 1, 1998; 161(1): 277 - 285. [Abstract] [Full Text] [PDF]

				S. L. Schauer, R. E. Bellas, and G. E. Sonenshein Dominant Signals Leading to Inhibitor {kappa}B Protein Degradation Mediate CD40 Ligand Rescue of WEHI 231 Immature B Cells from Receptor-Mediated Apoptosis J. Immunol., May 1, 1998; 160(9): 4398 - 4405. [Abstract] [Full Text] [PDF]

				K. Yamaoka, T. Otsuka, H. Niiro, Y. Arinobu, Y. Niho, N. Hamasaki, and K. Izuhara Activation of STAT5 by Lipopolysaccharide Through Granulocyte-Macrophage Colony-Stimulating Factor Production in Human Monocytes J. Immunol., January 15, 1998; 160(2): 838 - 845. [Abstract] [Full Text] [PDF]

				P. Saharinen, N. Ekman, K. Sarvas, P. Parker, K. Alitalo, and O. Silvennoinen The Bmx Tyrosine Kinase Induces Activation of the Stat Signaling Pathway, Which Is Specifically Inhibited by Protein Kinase Cdelta Blood, December 1, 1997; 90(11): 4341 - 4353. [Abstract] [Full Text] [PDF]

				S. J. Haque, Q. Wu, W. Kammer, K. Friedrich, J. M. Smith, I. M. Kerr, G. R. Stark, and B. R. G. Williams Receptor-associated constitutive protein tyrosine phosphatase activity controls the kinase function of JAK1 PNAS, August 5, 1997; 94(16): 8563 - 8568. [Abstract] [Full Text] [PDF]

				J. G. Karras, Z. Wang, L. Huo, R. G. Howard, D. A. Frank, and T. L. Rothstein Signal Transducer and Activator of Transcription-3 (STAT3) Is Constitutively Activated in Normal, Self-renewing B-1 Cells but Only Inducibly Expressed in Conventional B Lymphocytes J. Exp. Med., March 17, 1997; 185(6): 1035 - 1042. [Abstract] [Full Text] [PDF]

				S. Mahajan, A. Vassilev, N. Sun, Z. Ozer, C. Mao, and F. M. Uckun Transcription Factor STAT5A Is a Substrate of Bruton's Tyrosine Kinase in B Cells J. Biol. Chem., August 10, 2001; 276(33): 31216 - 31228. [Abstract] [Full Text] [PDF]