Cytokine-secreting follicular T cells shape the antibody repertoire

By R. Reinhardt, Hong-Erh Liang, R. Locksley. Nature Immunology, 2009

838 citations recorded by the source corpus.

High-affinity antibodies are critical for host protection and underlie successful vaccines. The generation of such antibodies requires T cell–dependent help, which mediates germinal center reactions in which mutation and selection of B cells occurs. Using an interleukin 4–reporter system, we show here that CD4+ follicular helper T cells constituted essentially all of the cytokine-secreting T cells in lymph nodes and were functionally distinct from T cells secreting the same cytokine in peripheral tissues. Follicular helper T cells with different cytokine profiles could be isolated as conjugates with B cells undergoing cytokine-specific immunoglobulin class switching with evidence of somatic hypermutation. Our findings support a model in which B cells compete for cytokines produced by follicular helper T cells that shape the affinity and isotype of the antibody response.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/da1add139108241d67e6f47061a76fca0ba98190

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Citations in the corpus

Differentiation of Effector CD4 T Cell Populations (2010, neutral): “In each instance, cells with the Tfh phenotype produced IL-4, and these cells could be shown to reside within germinal centers and to form contacts with responding B cells (32).”
Expanding roles for CD4+ T cells in immunity to viruses (2012, background): “Recent observations suggest that IL-4 and IFNγ produced by T FH cells have a central role in driving not only immunoglobulin class switching in the germinal centre, but also B cell affinity maturatio”
Follicular Helper T Cells. (2016, background): “IL-4 and IFN-γ, respectively, support class switching in mice to IgG1 or IgG2a, which can occur before or following GC formation (187, 188).”
Systemically dispersed innate IL-13–expressing cells in type 2 immunity (2010, background): “Despite these observations, these cytokines also have more dedicated functions during a type 2 response, with IL-4 facilitating humoral IgG1 and IgE production (3) and IL-13 contributing to epithelial hyperplasia and eosinophil recruitment in peripheral tissues (32).”
Bcl6 dependent T follicular helper cell differentiation diverges from effector cell differentiation during priming and depends on the gene Icos (2011, neutral): “Immunity 34, 932–946, June 24, 2011 ª2011 Elsevier Inc. 943 require Blimp1 for their full functionality (Kallies et al., 2009; Rutishauser et al., 2009).”
T follicular helper cell biology: A decade of discovery and diseases (2019, background): “The majority of IL-4 producing CD4+ T cells in LNs and spleen are Tfh cells, while Th2 cells are found in peripheral tissues (Reinhardt et al., 2009).”
IL-21 regulates germinal center B cell differentiation and proliferation through a B cell–intrinsic mechanism (2010, background): “This effect was, importantly, mediated by IL-21 acting directly on GC B cells and was not replicated by loss of IL-4.”
The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. (2009, background): “Indeed, few IFN-g-producing cells (compared with abundant IL-4 cells) were identified inside GCs in a recent study (Reinhardt et al., 2009); most were found outside peanut agglutininbinding areas.”
T follicular helper cell differentiation, function, and roles in disease (2014, neutral): “major-infected mice (Reinhardt et al., 2009).”
Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion (2011, background): “Th2-type Tfh cells were also demonstrated in mice (King and Mohrs, 2009; Reinhardt et al., 2009; Zaretsky et al., 2009).”