The capacity of Th2 lymphocytes to deliver B-cell help requires expression of the transcription factor STAT3.

CD4(+) T-cell help for B cells is crucial for effective Ab responses. Although follicular T helper (Tfh) cells have emerged as the main providers of T-cell help to B lymphocytes during the germinal center reaction, much less is known about the helper capacities of other effector CD4(+) T cells. The purpose of the present study was to evaluate the acquisition of B-cell help capacity of canonically derived T helper 2 (Th2) cells, a Th-cell subset originally considered responsible for B-cell help in vivo. We demonstrate herein that developing Th2 cells in mice co-express activated forms of signal transducer and activator of transcription 6 (STAT6) and STAT3 and that STAT3 expression was required for the capacity of Th2 cells to provide B-cell help. Thus, Th2 lymphocytes share a common, STAT3-mediated activation program for the acquisition of optimal B-cell help capacity with Tfh cells. Moreover, the expression of STAT3 in Th2 cells enhanced the IgG1-to-IgE class switch ratio in vivo, a finding with important implications for understanding the molecular basis of allergic diseases.

New role for hPar-1 kinases EMK and C-TAK1 in regulating localization and activity of class IIa histone deacetylases.

Class IIa histone deacetylases (HDACs) are found both in the cytoplasm and in the nucleus where they repress genes involved in several major developmental programs. In response to specific signals, the repressive activity of class IIa HDACs is neutralized through their phosphorylation on multiple N-terminal serine residues and 14-3-3-mediated nuclear exclusion. Here, we demonstrate that class IIa HDACs are subjected to signal-independent nuclear export that relies on their constitutive phosphorylation. We identify EMK and C-TAK1, two members of the microtubule affinity-regulating kinase (MARK)/Par-1 family, as regulators of this process. We further show that EMK and C-TAK1 phosphorylate class IIa HDACs on one of their multiple 14-3-3 binding sites and alter their subcellular localization and repressive function. Using HDAC7 as a paradigm, we extend these findings by demonstrating that signal-independent phosphorylation of the most N-terminal serine residue by the MARK/Par-1 kinases, i.e., Ser155, is a prerequisite for the phosphorylation of the nearby 14-3-3 site, Ser181. We propose that this multisite hierarchical phosphorylation by a variety of kinases allows for sophisticated regulation of class IIa HDACs function.

Myor/ABF-1 mRNA [corrected] Expression Marks Follicular Helper T Cells but Is Dispensable for Tfh Cell Differentiation and Function In Vivo.

Follicular T helper cells (Tfh) are crucial for effective antibody responses and long term T cell-dependent humoral immunity. Although many studies are devoted to this novel T helper cell population, the molecular mechanisms governing Tfh cell differentiation have yet to be characterized. MyoR/ABF-1 is a basic helix-loop-helix transcription factor that plays a role in the differentiation of the skeletal muscle and Hodgkin lymphoma. Here we show that MyoR mRNA is progressively induced during the course of Tfh-like cell differentiation in vitro and is expressed in Tfh responding to Alum-precipitated antigens in vivo. This expression pattern suggests that MyoR could play a role in the differentiation and/or function of Tfh cells. We tested this hypothesis using MyoR-deficient mice and found this deficiency had no impact on Tfh differentiation. Hence, MyoR-deficient mice developed optimal T-dependent humoral responses to Alum-precipitated antigens. In conclusion, MyoR is a transcription factor selectively up-regulated in CD4 T cells during Tfh cell differentiation in vitro and upon response to alum-protein vaccines in vivo, but the functional significance of this up-regulation remains uncertain.