BCL6b mediates the enhanced magnitude of the secondary response of memory CD8+ T lymphocytes.
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.
Manders
Peter M
PM
Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Cambridge CB2 2QH, UK.
Hunter
Patricia J
PJ
Telaranta
Aino I
AI
Carr
James M
JM
Marshall
Jennifer L
JL
Carrasco
Marlene
M
Murakami
Yusuke
Y
Palmowski
Michael J
MJ
Cerundolo
Vincenzo
V
Kaech
Susan M
SM
Ahmed
Rafi
R
Fearon
Douglas T
DT
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D017931:DNA Primers; D000939:Epitopes / Q000378:metabolism; D005260:Female; D040461:Gene Components; D018390:Gene Targeting; D005822:Genetic Vectors; D006182:H-Y Antigen / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008979:Moloney murine leukemia virus; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037941:Silencer Elements, Transcriptional / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology
C113027:Bcl6b protein, mouse; D017931:DNA Primers; D000939:Epitopes; D006182:H-Y Antigen; D007376:Interleukin-2; D012097:Repressor Proteins; D007371:Interferon-gamma