Michael Imbeault, Dave Blanger, Michel Ouellet, - PowerPoint PPT Presentation
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Michael Imbeault, Dave Blanger, Michel Ouellet,
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Michael Imbeault, Dave B langer, Michel Ouellet, Genevi ve Martin, Michel Tremblay. Centre de Recherche en Infectiologie, Ville de Qu bec, Canada. Universit Laval ... – PowerPoint PPT presentation
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Title: Michael Imbeault, Dave Blanger, Michel Ouellet,
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- Michael Imbeault, Dave Bélanger, Michel Ouellet,
- Geneviève Martin, Michel Tremblay
- Centre de Recherche en Infectiologie, Ville de
Québec, Canada - Université Laval
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- Polyclonal B cell activation
- Hypergammaglobulinemia
- Anergy
- Sensitivity to apoptosis
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- Efficient incorporation of membrane-bound host
molecules during budding - ICAM-1
- HLA-DR
- CD40L
- and many others
- These molecules are functional
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- Could HIV-1 particles bearing CD40L activate B
cells?
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- Morphological change
- Proliferation
- NF-kB activation
- Class switch recombination (CSR)
- IgM gt IgD, IgG, IgE, IgA
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- Primary B cells isolated from tonsils using
negative magnetic selection - Supplemented in IL-4 Il-10
- Lots of cells needed for microarray experiments
- 50-100 millions of cells
- More physiologically relevant than cell lines or
peripheral B cells
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Martin G al, J Virol, 2007
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- Efficient NF-kB translocation to the nucleus
- NL4.3/CD40L is comparable to PMA/Iono and
anti-CD40 (not shown)
Martin G al, J Virol, 2007
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- Gene expression analysis
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- Very similar genetic expression profiles between
HIV-1/CD40L and G28.5 at both time points - Most of the genes are associated to B cell
activation - Not much effect due to HIV alone (not shown)
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www.ambion.com
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8h
24h
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NL4-3 CD40L
Bal CD40L
Anti CD40
Mock CD40L
Mock
Bal
NL4-3
ICAM-1
Actin
Could be in part responsible for cellular
aggregation
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- Lymphotoxin A (TNF-b)
- Boosts proliferation of B cells
- Its upregulation has been characterized in
transient hypergammaglobulinemia - (Kowalczyk D, J Allergy Clin Immunol. 1997)
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Martin G al, J Virol, 2007
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www.ambion.com
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- Exposure of B cells to HIV-1 bearing CD40L
results in - Efficient polyclonal activation
- Isotype class switching
- Secretion of cytokines / chemokines
- Possible implications in B cells disorders seen
in some patients
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- Michel J. Tremblay
- Dave Bélanger
- Michel Ouellet
- Geneviève Martin
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