IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes

• Published in: Blood 2010-09, Vol.116 (10), p.1698-1704
• Main Authors: Séïté, Jean-François, Cornec, Divi, Renaudineau, Yves, Youinou, Pierre, Mageed, Rizgar A., Hillion, Sophie
• Format: Article
• Language: English
• Subjects: Apoptosis; Apoptosis - drug effects; B-Lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - drug effects; B-Lymphocytes - metabolism; Biological and medical sciences; Blotting, Western; Cell Cycle; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival; Cell Survival - drug effects; Cells, Cultured; Child; Dose-Response Relationship, Drug; Enzyme Activation; Enzyme Activation - drug effects; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Immunoglobulins, Intravenous; Immunoglobulins, Intravenous - chemistry; Immunoglobulins, Intravenous - metabolism; Immunoglobulins, Intravenous - pharmacology; Immunologic Factors; Immunologic Factors - chemistry; Immunologic Factors - metabolism; Immunologic Factors - pharmacology; Immunology; Life Sciences; Medical sciences; Microscopy, Confocal; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinase 3 - metabolism; N-Acetylneuraminic Acid; N-Acetylneuraminic Acid - chemistry; Protein Binding; Receptors, Antigen, B-Cell; Receptors, Antigen, B-Cell - metabolism; Sialic Acid Binding Ig-like Lectin 2; Sialic Acid Binding Ig-like Lectin 2 - metabolism; Signal Transduction; Signal Transduction - drug effects; Time Factors
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2009-12-261461

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 G1 phase. These changes may be accounted for the efficacy of IVIg in autoimmune diseases.