SA-IVIg targeting CD22 on B cells. BCR ligation initiates the activation of protein tyrosine kinases including Lyn, an Src family kinase that phosphorylates the ITAMs, leading to B-cell activation through cascade of kinase phosphorylation. Séïté et al¹  proved that SA-IVIg coligation to CD22 promotes apoptosis via inhibiting the cascade of kinase phosphorylation in mature human tonsil B lymphocytes and in human Ramos lymphoma B-cell lines by inducing phosphorylation of ITIM. IVIg-CD22 decreases BCR-mediated signaling through down-modulation of tyrosine phosphorylation of Lyn and recruitment and activation of phosphatase SHP-1, which can then down-modulate BCR-dependent pathways, regulating BLNK and PLCγ2 activation. The latter results in cell-cycle arrest and up-regulation of cascade, leading to apoptosis. BCR indicates B-cell receptor; ITAM, immunoreceptor tyrosine-based activation motif; ITIM, immunoreceptor tyrosine-based inhibitory motif; P, phosphorylation; SHP-1, Src homology 2 domain-containing phosphatase-1; BLNK, B-cell linker protein; and PLCγ, phospholipase Cγ2. Professional illustration by Debra T. Dartez.