ThF
Encyclopedia
Follicular B helper T cells (also known as just Follicular helper T cells or TFH), are antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

-experienced CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...

+ T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

s found in the B cell follicles of secondary lymphoid organs such as lymph nodes, spleens and Peyer's patches, and are identified by their constitutive expression of the B cell follicle homing receptor CXCR5
CXCR5
C-X-C chemokine receptor type 5 also known as Burkitt lymphoma receptor 1 is a G protein-coupled seven transmembrane receptor for chemokine CXCL13 and belongs to the CXC chemokine receptor family...

. TFH cells are found within B cell
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

 follicles and mediate antigen specific naïve or memory B cell activation, which triggers germinal center
Germinal center
Germinal centers are sites within lymph nodes where mature B lymphocytes rapidly proliferate, differentiate, mutate their antibodies , and class switch their antibodies during a normal immune response to an infection...

 formation, probably through the expression of CD40L and the secretion of IL-21
IL-21
IL-21 or IL 21 can refer to:* Interleukin 21* Illinois' 21st congressional district, an obsolete district* Illinois Route 21...

 and IL-4. It is possible that TFH cells might arise as branches in the Th1 and Th2 differentiation pathways but their precise lineage relationship to the other effector CD4+ T cell subsets is still uncertain. Recent studies have however shown that TFH have distinct gene expression profiles, supporting the theory that TFH are a subset of CD4+ T cells distinct from Th-1, Th-2, Th-17
T helper 17 cell
T helper 17 cells are a subset of T helper cells producing interleukin 17 discovered in 2007. They are considered developmentally distinct from Th1 and Th2 cells and excessive amounts of the cell are thought to play a key role in autoimmune disease such as multiple sclerosis , but also...

 or Tregs
Regulatory T cell
Regulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...

.

Role of ICOS

The Inducible T-cell co-stimulator
CD278
Inducible T-cell costimulator is a protein that in humans is encoded by the ICOS gene.CD278 or ICOS is a CD28-superfamily costimulatory molecule that is expressed on activated T cells...

 (CD278 or ICOS) has proven to provide a particularly critical signal for TFH cells since mice deficient in ICOS are unable to develop any TFH, although the exact mechanisms involved are as of yet unknown. However, it was shown that ICOS induces the secretion of IL-21 by activated CD4+ T cells and that IL-21 plays a crucial role in the development of TFH. Also Bcl-6
BCL6
B-cell lymphoma 6 protein is a protein that in humans is encoded by the BCL6 gene.- Function :The protein encoded by this gene is an evolutionarily conserved zinc finger transcription factor and contains an N-terminal POZ/BTB domain...

 is a transcription factor identified in TFH cells, but it may have roles that extend beyond this subset, because it has been implicated in memory CD8+
Cytotoxic T cell
A cytotoxic T cell belongs to a sub-group of T lymphocytes that are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with viruses , or are otherwise damaged or...

T cell development..

Autoimmunity

Finally, it has been shown that dysregulated TFH cells can cause systemic autoimmunity and auto-antibody production or contribute to T cell–mediated organ-specific autoimmunity.
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