BCL6b mediates the enhanced magnitude of the secondary response of memory CD8+ T lymphocytes

Proc Natl Acad Sci U S A. 2005 May 24;102(21):7418-25. doi: 10.1073/pnas.0501585102. Epub 2005 Apr 15.


A characteristic of the secondary response of CD8(+) T cells that distinguishes it from the primary response is the generation of greater numbers of effector cells. Because effector CD8(+) T cells are derived from a pool of less differentiated, replicating cells in secondary lymphoid organs, and because IL-2 mediates effector differentiation, the enhanced secondary response may reflect the enlargement of this generative pool by the transient repression of IL-2-mediated differentiation. We have examined for this function the transcriptional repressor BCL6b, a homologue of BCL6 that represses IL-2-induced B cell differentiation. BCL6b is expressed in a small subset of antigen-experienced CD8(+) T cells. Ectopic expression of BCL6b in CD8(+) T cells diminishes their growth in response to IL-2 in vitro. Female mice in which the BCL6b gene has been interrupted have normal primary responses of CD8(+) T cells to infection with vaccinia expressing the H-Y epitope, Uty, but Uty-specific, BCL6b(-/-), memory CD8(+) T cells have diminished recall proliferative responses to this epitope in vitro. BCL6b(-/-) mice also have normal primary CD8(+) T cell responses to influenza infection, but nucleoprotein peptide-specific, BCL6b(-/-), memory CD8(+) T cells have a cell autonomous defect in the number of effector cells generated in response to reinfection. Therefore, BCL6b is required for the enhanced magnitude of the secondary response of memory CD8(+) T cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • DNA Primers
  • Epitopes / metabolism
  • Female
  • Gene Components
  • Gene Targeting
  • Genetic Vectors
  • H-Y Antigen / metabolism
  • Humans
  • Immunologic Memory*
  • Interferon-gamma / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Mice
  • Mice, Knockout
  • Moloney murine leukemia virus
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Silencer Elements, Transcriptional / immunology*
  • Vaccinia / immunology


  • Bcl6b protein, mouse
  • DNA Primers
  • Epitopes
  • H-Y Antigen
  • Interleukin-2
  • Repressor Proteins
  • Interferon-gamma