title: Human T follicular helper cells in primary immunodeficiencies.
abstract: OBJECTIVE
  To summarize our understanding of the biology of T follicular helper (Tfh) cells and how insights into this are being provided by the study of human monogenic immunological diseases.
  
  
  RESULTS
  Antibody production is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. Long-lived humoral immunity depends on help provided by Tfh cells, which support the differentiation of antigen-specific B cells into memory and plasma cells. Tfh cells are generated from naïve CD4 T cells following the receipt of inputs from various cell surface receptors. Although genetically modified mice have provided a great understanding of the requirements for generating Tfh cells, it is critical that the requirements for human Tfh cells are also established. This is being achieved by the systematic analysis of humans with monogenic mutations that cause primary immunodeficiencies characterized by impaired humoral immunity following infection or vaccination.
  
  
  CONCLUSIONS
  The elucidation of the mechanisms that regulate Tfh cell generation, differentiation and function should reveal targets for novel therapeutics that may offer opportunities to manipulate these cells to not only improve humoral immunity in the setting of primary immunodeficiencies but also temper their dysregulation in conditions of antibody-mediated autoimmunity.
authors.affiliation: aImmunology Division, Garvan Institute of Medical Research, Darlinghurst bSt Vincent's Clinical School, University of New South Wales, Kensington, New South Wales, Australia cLaboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Cindy S
authors.initials: CS
authors.lastname: Ma
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
mesh_terms: D002648:Child; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*