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Flice-Inhibitory protein is a key regulator of germinal center B cell apoptosis

Affinity maturation of the B cell response to antigen (Ag) takes place in the germinal centers (GCs) of secondary follicles. Two sequential molecular mechanisms underpin this process. First, the B cell repertoire is diversified through hypermutation of the immunoglobulin (Ig) variable region genes....

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Bibliographische Detailangaben
Hauptverfasser: Hennino, Ana (VerfasserIn) , Krammer, Peter H. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 19, 2001
In: Journal of experimental medicine
Year: 2001, Jahrgang: 193, Heft: 4, Pages: 447-458
ISSN:1540-9538
DOI:10.1084/jem.193.4.447
Online-Zugang:Verlag, Volltext: https://doi.org/10.1084/jem.193.4.447
Verlag, Volltext: https://rupress.org/jem/article/193/4/447/20066/Flice-Inhibitory-Protein-Is-a-Key-Regulator-of
Volltext
Verfasserangaben:by Ana Hennino, Marion Bérard, Peter H. Krammer and Thierry Defrance
Beschreibung
Zusammenfassung:Affinity maturation of the B cell response to antigen (Ag) takes place in the germinal centers (GCs) of secondary follicles. Two sequential molecular mechanisms underpin this process. First, the B cell repertoire is diversified through hypermutation of the immunoglobulin (Ig) variable region genes. Second, mutant B cell clones with improved affinity for Ag are positively selected by Ag and CD40 ligand (L). This selection step is contingent upon “priming” of GC B cells for apoptosis. The molecular means by which B cell apoptosis is initiated and controled in the GC remains unclear. Here, we show that GC B cell apoptosis is preceded by the rapid activation of caspase-8 at the level of CD95 death-inducing signaling complex (DISC). We found that GC B cells ex vivo display a preformed inactive DISC containing Fas-associated death domain-containing protein (FADD), procaspase-8, and the long isoform of cellular FADD-like IL-1β-converting enzyme-inhibitory protein (c-FLIPL) but not the CD95L. In culture, c-FLIPL is rapidly lost from the CD95 DISC unless GC B cells are exposed to the survival signal provided by CD40L. Our results suggest that (a) the death receptor signaling pathway is involved in the affinity maturation of antibodies, and (b) c-FLIPL plays an active role in positive selection of B cells in the GC.
Beschreibung:Gesehen am 26.04.2021
Beschreibung:Online Resource
ISSN:1540-9538
DOI:10.1084/jem.193.4.447

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