Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/828
Title: Inhibition of Terminal Differentiation of B Cells Mediated by CD27 and CD40 Involves Signaling through JNK
Authors: George, Anna
Satpathy, Shuchismita
Shenoy, Gautam N
Kaw, Sheetal
Vaidya, Tushar
Bal, Vineeta
Rath, Satyajit
Issue Date: Dec-2010
Publisher: The American Association of Immunologists, Inc
Abstract: B cells responding to cognate Ag in vivo undergo clonal expansion that is followed by differentiation into Ab-secreting plasma cells or into quiescent restimulable memory. Both these events occur in the germinal center and require that cells exit from proliferation, but the signals that lead to one or the other of these mutually exclusive differentiation pathways have not been definitively characterized. Previous experiments have shown that signals transduced through the TNFRs CD27 and CD40 at the time of B cell stimulation in vitro or in vivo can influence this cell fate decision by inhibiting terminal differentiation and promoting memory. In this study, we show that the PIQED domain of the cytoplasmic tail of murine CD27 and the adapter molecule TNFR-associated factor 2 are involved in this effect. Using pharmacological inhibitors of signaling intermediates, we identify JNK as being necessary and sufficient for the observed inhibition of terminal differentiation. While JNK is involved downstream of CD40, inhibition of the MEK pathway can also partially restore plasma cell generation, indicating that both signaling intermediates may be involved. We also show that inhibition of induction of IFN regulatory factor 4 and B lymphocyte induced maturation protein 1 are downstream events common to both receptors.
URI: http://hdl.handle.net/123456789/828
Appears in Collections:Mucosal Immunology, Publications

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