T-follicular helper cell differentiation and the co-option of this pathway by non-helper cells

Michelle A. Linterman*, Adrian Liston, Carola G. Vinuesa

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    77 Citations (Scopus)

    Abstract

    Human and mouse studies performed over the last decade have established that follicular helper T (Tfh) cells are a CD4 + helper subset specialized in the provision of help to B cells. Tfh differentiation is driven by expression of the transcriptional repressor B-cell lymphoma-6 (Bcl-6), which turns on a program that guides T cells close to B-cell areas where Tfh cells first provide help to B cells. Sustained Bcl-6 expression promotes the entry of Tfh cells into follicles and modulates their cytokine expression profile so they can support and select germinal center B cells that have acquired affinity-enhancing mutations in their immunoglobulin genes. Forkhead box 3 protein (Foxp3) + regulatory T cells and invariant natural killer T (NKT) cells can also co-opt the Bcl-6-dependent follicular differentiation pathway to migrate into B-cell follicles and regulate antibody responses. The resulting NKT follicular helper cells drive a distinctive type of T-dependent B-cell response to lipid-containing antigens, whereas FoxP3 + follicular regulatory (Tfr) cells exert a suppressive function on germinal centers. Elucidating how Tfr cells are functionally and numerically regulated and the factors that control the balance between Tfh and Tfr cells is likely to be critical for improved understanding of the pathogenesis and progression of autoimmunity and lymphomas of germinal center origin, and generation of effective vaccines.

    Original languageEnglish
    Pages (from-to)143-159
    Number of pages17
    JournalImmunological Reviews
    Volume247
    Issue number1
    DOIs
    Publication statusPublished - May 2012

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