IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses

Michelle A. Linterman, Laura Beaton, Di Yu, Roybel R. Ramiscal, Monika Srivastava, Jennifer J. Hogan, Naresh K. Verma, Mark J. Smyth, Robert J. Rigby, Carola G. Vinuesa

    Research output: Contribution to journalArticlepeer-review

    619 Citations (Scopus)

    Abstract

    During T cell-dependent responses, B cells can either differentiate extrafollicularly into short-lived plasma cells or enter follicles to form germinal centers (GCs). Interactions with T follicular helper (Tfh) cells are required for GC formation and for selection of somatically mutated GC B cells. Interleukin (IL)-21 has been reported to play a role in Tfh cell formation and in B cell growth, survival, and isotype switching. To date, it is unclear whether the effect of IL-21 on GC formation is predominantly a consequence of this cytokine acting directly on the Tfh cells or if IL-21 directly influences GC B cells. We show that IL-21 acts in a B cell-intrinsic fashion to control GC B cell formation. Mixed bone marrow chimeras identified a significant B cell-autonomous effect of IL-21 receptor (R) signaling throughout all stages of the GC response. IL-21 deficiency profoundly impaired affinity maturation and reduced the proportion of IgG1+ GC B cells but did not affect formation of early memory B cells. IL-21R was required on GC B cells for maximal expression of Bcl-6. In contrast to the requirement for IL-21 in the follicular response to sheep red blood cells, a purely extrafollicular antibody response to Salmonella dominated by IgG2a was intact in the absence of IL-21.

    Original languageEnglish
    Pages (from-to)353-363
    Number of pages11
    JournalJournal of Experimental Medicine
    Volume207
    Issue number2
    DOIs
    Publication statusPublished - 15 Feb 2010

    Fingerprint

    Dive into the research topics of 'IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses'. Together they form a unique fingerprint.

    Cite this