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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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
February 19, 2001
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| 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 
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| Verfasserangaben: | by Ana Hennino, Marion Bérard, Peter H. Krammer and Thierry Defrance |
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| 520 | |a 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. | ||
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