IL-4 Upregulates Igα and Igβ Protein, Resulting in Augmented IgM Maturation and B Cell Receptor–Triggered B Cell Activation
作者： Benchang Guo , Thomas L. Rothstein
关键词:
摘要: IL-4 is critical for optimal B cell activation and germinal center expansion in T-dependent immune responses; however, the underlying mechanism remains elusive. In current study, we found that primary cells express little Igα Igβ protein despite substantial levels of mRNA. markedly upregulates expression requires STAT6. Elevated form heterodimers associate with IgM significantly promote maturation surface expression, resulting amplified BCR-initiated signaling Lyn dependent. vivo, pregerminal upregulated Igα, Igβ, conjunction elevated BCR-triggered phosphorylated ERK ex are dependent on reversed by vivo administration neutralizing anti–IL-4 Ab. Thus, this study elucidates a novel cross-talk between BCRs programs enhancement subsequent BCR signaling.
jimmunol.org参考文章(44)
J. Hombach, L. Leclercq, A. Radbruch, K. Rajewsky, M. Reth, A novel 34-kd protein co-isolated with the IgM molecule in surface IgM-expressing cells. The EMBO Journal. ,vol. 7, pp. 3451- 3456 ,(1988) , 10.1002/J.1460-2075.1988.TB03219.X
Alexander J. McAdam, Rebecca J. Greenwald, Michele A. Levin, Tatyana Chernova, Nelly Malenkovich, Vincent Ling, Gordon J. Freeman, Arlene H. Sharpe, ICOS is critical for CD40-mediated antibody class switching Nature. ,vol. 409, pp. 102- 105 ,(2001) , 10.1038/35051107
Isharat Yusuf, Robin Kageyama, Laurel Monticelli, Robert J. Johnston, Daniel DiToro, Kyle Hansen, Burton Barnett, Shane Crotty, Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150). Journal of Immunology. ,vol. 185, pp. 190- 202 ,(2010) , 10.4049/JIMMUNOL.0903505
Margaret L. Hibbs, David M. Tarlinton, Jane Armes, Dianne Grail, George Hodgson, Rosemarie Maglitto, Steven A. Stacker, Ashley R. Dunn, Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease Cell. ,vol. 83, pp. 301- 311 ,(1995) , 10.1016/0092-8674(95)90171-X
Bazarragchaa Damdinsuren, Yongqing Zhang, Ashraf Khalil, William H. Wood, Kevin G. Becker, Mark J. Shlomchik, Ranjan Sen, Single Round of Antigen Receptor Signaling Programs Naive B Cells to Receive T Cell Help Immunity. ,vol. 32, pp. 355- 366 ,(2010) , 10.1016/J.IMMUNI.2010.02.013
Christopher C. Goodnow, Jeffrey Crosbie, Stephen Adelstein, Thomas B. Lavoie, Sandra J. Smith-Gill, Robert A. Brink, Helen Pritchard-Briscoe, John S. Wotherspoon, Robert H. Loblay, Kathy Raphael, Ronald J. Trent, Antony Basten, Altered immunoglobulin expression and functional silencing of self-reactive B lymphocytes in transgenic mice Nature. ,vol. 334, pp. 676- 682 ,(1988) , 10.1038/334676A0
SJ Fleire, JP Goldman, YR Carrasco, M Weber, D Bray, FD Batista, B cell ligand discrimination through a spreading and contraction response. Science. ,vol. 312, pp. 738- 741 ,(2006) , 10.1126/SCIENCE.1123940
L. Matsuuchi, M. R. Gold, A. Travis, R. Grosschedl, A. L. DeFranco, R. B. Kelly, The membrane IgM-associated proteins MB-1 and Ig-beta are sufficient to promote surface expression of a partially functional B-cell antigen receptor in a nonlymphoid cell line. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 89, pp. 3404- 3408 ,(1992) , 10.1073/PNAS.89.8.3404
Adam F. Cunningham, Karine Serre, Kai-Michael Toellner, Mahmood Khan, James Alexander, Frank Brombacher, Ian C. M. MacLennan, Pinpointing IL-4-independent acquisition and IL-4-influenced maintenance of Th2 activity by CD4 T cells European Journal of Immunology. ,vol. 34, pp. 686- 694 ,(2004) , 10.1002/EJI.200324510
Masahiro Kitano, Saya Moriyama, Yoshikazu Ando, Masaki Hikida, Yasuo Mori, Tomohiro Kurosaki, Takaharu Okada, Bcl6 Protein Expression Shapes Pre-Germinal Center B Cell Dynamics and Follicular Helper T Cell Heterogeneity Immunity. ,vol. 34, pp. 961- 972 ,(2011) , 10.1016/J.IMMUNI.2011.03.025