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

Jean-François Séïté (1) , Divi Cornec (1, 2) , Yves Renaudineau (1, 3) , Pierre Youinou (1, 3) , Rizgar A Mageed (4) , Sophie Hillion (1, 5)

1 EA2216 - Immunologie et Pathologie
2 CHU - BREST - Rhumato - CHRU Brest - Service de Rhumatologie
3 Laboratoire d'Immunologie et Immunothérapie
4 William Harvey Research Institute, Barts and the London Medical School
5 LabEX IGO Immunothérapie Grand Ouest

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.

Domaines: Immunologie

Jean-François Séïté, Divi Cornec, Yves Renaudineau, Pierre Youinou, Rizgar A Mageed, et al.. IVIg modulates BCR signaling through CD22 and promotes apoptosis in mature human B lymphocytes.. Blood, 2010, 116 (10), pp.1698-704. ⟨10.1182/blood-2009-12-261461⟩. ⟨hal-01150519⟩