Abstract Upon infection or immunization, dendritic cells (DCs) present antigens (Ags) to naïve CD4 +T cells. As a result, fraction of the responding upregulate Bcl6 and differentiate into T follicular helper (Tfh) cells, which migrate B cell follicles. Once in follicles, Tfh help promote development maintenance germinal centers (GC). Importantly, limiting number is critical for maintaining sele...

T follicular helper (Tfh) cells are essential for efficient B cell responses, yet the factors that regulate differentiation of this CD4(+) T cell subset are incompletely understood. Here we found that the KLF2 transcription factor serves to restrain Tfh cell generation. Induced KLF2 deficiency in activated CD4(+) T cells led to increased Tfh cell generation and B cell priming, whereas KLF2 over...

Abstract IL-6 is an important signal three cytokine for T helper 17 (Th17) and follicular (Tfh) differentiation. Previous work has suggested a possible role TRAF3 in the function and/or differentiation of these two subsets, but no direct studies have yet been performed. In this study, we examine IL-6R signaling cells. regulates IL-2R type I interferon receptor cells by altering recruitment phos...

The production of high affinity, class switched antibodies produced by B cells hinges on the effective differentiation of T follicular helper (Tfh) cells. Here we define conditions specifically enhancing Tfh differentiation and providing protection in a model of influenza infection. Tfh responses were associated with prolonged antigen presentation by dendritic cells (DCs), which maintained T ce...

Follicular T helper (Tfh) cells are recognized by the expression of CXCR5 and the transcriptional regulator Bcl-6. Tfh cells control B cell maturation and antibody production, and if deregulated, may lead to autoimmunity. Here, we study the role of the proto-oncogene survivin in the formation of Tfh cells. We show that blood Tfh cells of patients with the autoimmune condition rheumatoid arthrit...

T follicular helper (Tfh) cells are involved in specific humoral immunity at initial and recall phases. The fact that the transcription repressors B-cell lymphoma-6 and Blimp-1 determine lineages of Tfh cells and other types of effector CD4(+) T cells, respectively, suggests that there are unique mechanisms to establish Tfh-cell identity. In this study, we found that Tfh cells preferentially ex...

CD4(+) T follicular helper cells (TFH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21, and IL-12 can promote TFH cell formation. Yet, none of the...

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...

Germinal centers (GC) are specialized anatomic sites where B cells undergo somatic hypermutation, clonal expansion, and affinity-based selection. Stringent regulation of GC reactions is critical for homeostatic B cell development, as well as T-dependent humoral immunity against self and foreign antigens. Follicular helper T cells (Tfh, CXCR5PDBcl-6CD4) that reside in GC serve as specialized B h...

In primary humoral responses, B-cell lymphoma 6 (Bcl6) is a master regulator of follicular helper T (TFH) cell differentiation; however, its activation mechanisms and role in memory responses remain unclear. Here we demonstrate that survival of CXCR5(+) TFH memory cells, and thus subsequent recall antibody response, require Bcl6 expression. Furthermore, we show that, upon rechallenge with solub...