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Following infection, inflammatory cues upregulate core transcriptional programs to establish pathogen-specific protection. In viral infections, T follicular helper (TFH) cells express the prototypical T helper 1 transcription factor T-bet. Several studies have demonstrated essential but conflicting roles for T-bet in TFH biology. Understanding the basis of this controversy is crucial, as modulation of T-bet expression instructs TFH differentiation and ultimately protective antibody responses. Comparing influenza and LCMV viral infections, we demonstrate that the role of T-bet is contingent on the environmental setting of TFH differentiation, IL-2 signaling, and T cell competition. Furthermore, we demonstrate that T-bet expression by either TFH or GC B cells independently drives antibody isotype class switching. Specifically, T cell-specific loss of T-bet promotes IgG1, whereas B cell-specific loss of T-bet inhibits IgG2a/c switching. Combined, this work highlights that the context-dependent induction of T-bet instructs the development of protective, neutralizing antibodies following viral infection or vaccination.
This article was published in the following journal.
Name: Cell reports
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The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.
Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES.
A growth differentiation factor that plays a role in the genesis of left-right asymmetry during vertebrate development. Evidence for this role is seen in MICE where loss of growth differentiation factor 1 function results in right-left isomerism of visceral organs. In HUMANS heterozygous loss of growth differentiation factor 1 function has been associated with CONGENITAL HEART DEFECTS and TRANSPOSITION OF GREAT VESSELS.
The period of the MENSTRUAL CYCLE representing follicular growth, increase in ovarian estrogen (ESTROGENS) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of MENSTRUATION and ends with OVULATION.
A growth differentiation factor that plays a role in the neural differentiation, specifically in the retinal development of the EYE.
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...
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