Hegerl_and_Solomon_2009_Science[1]

Hegerl_and_Solomon_2009_Science[1] - PERSPECTIVES cells to...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
www.sciencemag.org SCIENCE VOL 325 21 AUGUST 2009 955 PERSPECTIVES a critical determinant of T FH cell generation. It will be interesting to see how different envi- ronmental cues affect the balance between these two transcriptional antagonists. Uncontrolled generation of T FH cells could be fatal, causing systemic autoimmunity by increasing antibody production. Therefore, expression of Blimp-1 may help maintain tol- erance by inhibiting Bcl6 expression and the differentiation of T FH cells. But if Bcl6 sup- presses the generation of T H 1 and T H 17 cells by binding to their master transcription fac- tors, then how are B cells stimulated to pro- duce antibodies in response to inteferon- γ and IL-17, the cytokines that these T cell subtypes secrete? One possibility is that B cells are induced to make these antibodies by T H 1 and T H 17 cells, instead of T FH cells, outside of ger- minal centers ( 13 ). Alternatively, differentiat- ing T H 1, T H 2, and T H 17 cells may express low amounts of Bcl6, which might allow them to acquire the T FH cell phenotype and induce B cells to make these antibodies. Johnston et al . show that a T cell–B cell interaction is essen- tial for Bcl6 expression in activated CD4 + T cells, which in turn could initiate differentia- tion into T FH cells. It might be possible that activated T H 1, T H 2, and T H 17 cells express Bcl6 upon interaction with B cells, causing them to become T FH 1, T FH 2, and T FH 17 cells. They could then affect antibody production by B cells through the cytokines they produce. The transcription factor cMaf also plays an essential role in generating T FH cells ( 14 ). cMaf primarily activates IL-21 expression in CD4 + T cells, and thus provides an auto- crine growth factor for T FH cell development ( 15 ). Bcl6 and cMaf may synergize to gen- erate T FH cells by regulating the expression of critical factors such as IL-21, the IL-21 receptor, and CXCR5. The balance among the transcription factors in the differentia- tion of T FH cells, particularly between Bcl6 and Blimp-1, could be exploited in various autoimmune and infectious diseases. References and Notes 1. L. J. McHeyzer-Williams, M. G. McHeyzer-Williams, Annu. Rev. Immunol. 23 , 487 (2005). 2. R. J. Johnston et al ., Science 325 , 1006 (2009); published online 16 July 2009 (10.1126/science. 1175870). 3. R. I. Nurieva et al, Science 325 , 1001 (2009); published online 23 July 2009 (10.1126/science. 1176676). 4. D. Yu et al ., Immunity 10.1016/j.immuni.2009.07.002 (2009). 5. N. Fazilleau et al ., Immunity 30 , 324 (2009). 6. A. G. Zaretsky et al ., J. Exp. Med. 206 , 991 (2009). 7. T. Korn et al ., Nature 448 , 484 (2007). 8. R. Nurieva et al ., Nature 448 , 480 (2007). 9. R. I. Nurieva
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

Page1 / 2

Hegerl_and_Solomon_2009_Science[1] - PERSPECTIVES cells to...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online