Contrasting cytoskeletal regulation of MHC class II peptide presentation by human B cells or dendritic cells.
MHC class II-mediated antigen presentation by B lymphocytes or dendritic cells (DC) initiates CD4+ T lymphocyte activation. In B lymphocytes, MHC class II peptide presentation has been characterised by recruitment of MHC class II, F-actin and lipid rafts to the B cell-T cell immunological synapse. We now show that MHC class II engagement in B lymphocytes induced lipid raft-independent Rho and Rac activation and that inhibition of either Rho-GTPase activation or actin polymerisation in the B cell abrogated T cell activation without altering B cell-T cell conjugate formation. Short-hairpin RNA studies excluded a role for the Cdc42 effector Wiskott-Aldrich syndrome protein. In contrast, antigen presentation by DC was Rho-GTPase-independent although actin was recruited to the DC-T cell interaction site. Moreover, actin depolymerisation in the DC significantly increased T cell activation without altering the number of DC-T cell conjugates. Finally we show that stable recruitment of HLA-DR to the site of the immunological synapse is not a uniform observation in DC and demonstrate reduced HLA-DR expression at the site of microtubule organising centre polarization. Therefore although actin accumulates in DC and B lymphocytes at the immunological synapse with antigen-specific T lymphocytes, this does not reflect comparable functional roles of their actin cytoskeletons in antigen presentation.
Delaguillaumie
Alix
A
INSERM Unité 662 Paris, Institut Universitaire d'Hématologie, Université Paris-Diderot, Faculté de Médecine, Hôpital Saint-Louis, Paris, France.
Marin-Esteban
Viviana
V
Setterblad
Niclas
N
Leh
Laurence Jeanson
LJ
Assier
Eric
E
Gelin
Catherine
C
Charron
Dominique
D
Galy
Anne
A
Mooney
Nuala
N
D000199:Actins / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004789:Enzyme Activation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D021962:Membrane Microdomains / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D051316:Wiskott-Aldrich Syndrome Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins