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IL-21 and IL-4 Collaborate To Shape T-Dependent Antibody Responses.
McGuire, Helen M; Vogelzang, Alexis; Warren, Joanna; Loetsch, Claudia; Natividad, Karlo D; Chan, Tyani D; Brink, Robert; Batten, Marcel; King, Cecile.
Afiliación
  • McGuire HM; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Vogelzang A; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Warren J; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and.
  • Loetsch C; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Natividad KD; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and.
  • Chan TD; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Brink R; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • Batten M; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia.
  • King C; Department of Immunology, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia; and St. Vincent's Clinical School, University of New South Wales, Sydney, New South Wales 2052, Australia c.king@garvan.org.au.
J Immunol ; 195(11): 5123-35, 2015 Dec 01.
Article en En | MEDLINE | ID: mdl-26491200
The selection of affinity-matured Ab-producing B cells is supported by interactions with T follicular helper (Tfh) cells. In addition to cell surface-expressed molecules, cytokines produced by Tfh cells, such as IL-21 and IL-4, provide B cell helper signals. In this study, we analyze how the fitness of Th cells can influence Ab responses. To do this, we used a model in which IL-21R-sufficient (wild-type [WT]) and -deficient (Il21r(-/-)) Ag-specific Tfh cells were used to help immunodeficient Il21r(-/-) B cells following T-dependent immunization. Il21r(-/-) B cells that had received help from WT Tfh cells, but not from Il21r(-/-) Tfh cells, generated affinity-matured Ab upon recall immunization. This effect was dependent on IL-4 produced in the primary response and associated with an increased fraction of memory B cells. Il21r(-/-) Tfh cells were distinguished from WT Tfh cells by a decreased frequency, reduced conjugate formation with B cells, increased expression of programmed cell death 1, and reduced production of IL-4. IL-21 also influenced responsiveness to IL-4 because expression of both membrane IL-4R and the IL-4-neutralizing soluble (s)IL-4R were reduced in Il21r(-/-) mice. Furthermore, the concentration of sIL-4R was found to correlate inversely with the amount of IgE in sera, such that the highest IgE levels were observed in Il21r(-/-) mice with the least sIL-4R. Taken together, these findings underscore the important collaboration between IL-4 and IL-21 in shaping T-dependent Ab responses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Interleucinas / Interleucina-4 / Linfocitos T Colaboradores-Inductores / Subunidad alfa del Receptor de Interleucina-21 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Interleucinas / Interleucina-4 / Linfocitos T Colaboradores-Inductores / Subunidad alfa del Receptor de Interleucina-21 Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: J Immunol Año: 2015 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos