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Publication : B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells.

First Author  Lee SK Year  2011
Journal  J Exp Med Volume  208
Issue  7 Pages  1377-88
PubMed ID  21708925 Mgi Jnum  J:325691
Mgi Id  MGI:6205837 Doi  10.1084/jem.20102065
Citation  Lee SK, et al. (2011) B cell priming for extrafollicular antibody responses requires Bcl-6 expression by T cells. J Exp Med 208(7):1377-88
abstractText  T follicular helper cells (Tfh cells) localize to follicles where they provide growth and selection signals to mutated germinal center (GC) B cells, thus promoting their differentiation into high affinity long-lived plasma cells and memory B cells. T-dependent B cell differentiation also occurs extrafollicularly, giving rise to unmutated plasma cells that are important for early protection against microbial infections. Bcl-6 expression in T cells has been shown to be essential for the formation of Tfh cells and GC B cells, but little is known about its requirement in physiological extrafollicular antibody responses. We use several mouse models in which extrafollicular plasma cells can be unequivocally distinguished from those of GC origin, combined with antigen-specific T and B cells, to show that the absence of T cell-expressed Bcl-6 significantly reduces T-dependent extrafollicular antibody responses. Bcl-6(+) T cells appear at the T-B border soon after T cell priming and before GC formation, and these cells express low amounts of PD-1. Their appearance precedes that of Bcl-6(+) PD-1(hi) T cells, which are found within the GC. IL-21 acts early to promote both follicular and extrafollicular antibody responses. In conclusion, Bcl-6(+) T cells are necessary at B cell priming to form extrafollicular antibody responses, and these pre-GC Tfh cells can be distinguished phenotypically from GC Tfh cells.
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