IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes.
Among various mechanisms for interactions with B cells, intravenous immunoglobulin (IVIg) may operate through the insertion of its Fc part into the Fc-γ receptor, or the binding of its sialic acid (SA)-bearing glycans to the negatively regulating CD22 lectin. It appeared that IVIg reduces B lymphocyte viability in a dose- and time-dependent manner. Furthermore, we show by confocal microscopy that SA-positive IgG, but not SA-negative IgG bind to CD22. This interaction reduces the strength of B-cell receptor-mediated signaling trough down-regulating tyrosine phosphorylation of Lyn and the B-cell linker proteins, and up-regulating phospholipase Cγ2 activation. This cascade resulted in a sustained activation of Erk 1/2 and arrest of the cell cycle at the G(1) phase. These changes may be accounted for the efficacy of IVIg in autoimmune diseases.
EA2216 Immunology and Pathology and Institut Fédératif de Recherche 148, Université de Bretagne Occidentale, Brest, France.
Jean-François
JF
Séïté
Divi
D
Cornec
Yves
Y
Renaudineau
Pierre
P
Youinou
Rizgar A
RA
Mageed
Sophie
S
Hillion
D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007155:Immunologic Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019158:N-Acetylneuraminic Acid