21 AUGUST 2009
a critical determinant of T
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
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
cells. But if Bcl6 sup-
presses the generation of T
1 and T
by binding to their master transcription fac-
tors, then how are B cells stimulated to pro-
duce antibodies in response to inteferon-
IL-17, the cytokines that these T cell subtypes
secrete? One possibility is that B cells are
induced to make these antibodies by T
17 cells, instead of T
cells, outside of ger-
minal centers (
). Alternatively, differentiat-
2, and T
17 cells may express low
amounts of Bcl6, which might allow them to
acquire the T
cell phenotype and induce B
cells to make these antibodies. Johnston
show that a T cell–B cell interaction is essen-
tial for Bcl6 expression in activated CD4
cells, which in turn could initiate differentia-
tion into T
cells. It might be possible that
2, and T
17 cells express
Bcl6 upon interaction with B cells, causing
them to become T
2, and T
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
cMaf primarily activates IL-21 expression
T cells, and thus provides an auto-
crine growth factor for T
). Bcl6 and cMaf may synergize to gen-
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-
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.
, 487 (2005).
2. R. J. Johnston
, 1006 (2009);
published online 16 July 2009 (10.1126/science.
3. R. I. Nurieva
, 1001 (2009);
published online 23 July 2009 (10.1126/science.
4. D. Yu
5. N. Fazilleau
, 324 (2009).
6. A. G. Zaretsky
J. Exp. Med.
, 991 (2009).
7. T. Korn
, 484 (2007).
8. R. Nurieva
, 480 (2007).
9. R. I. Nurieva