title: CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling.
abstract: A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can downmodulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in α2,6 linkages in cis, on the surface of the same B cell or in trans, on other cells. Sialic acids are self ligands, as they are abundant in vertebrates, but are usually not expressed by pathogens. We show that cis-ligand binding of CD22 is crucial for the regulation of B-cell Ca(2+) signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca(2+) signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca(2+) responses, increased B-cell turnover, and impaired survival of the B cells. Thus, the CD22 ligand-binding domain has a crucial function in regulating BCR signaling, which is relevant for controlling autoimmunity.
authors.affiliation: Department of Biology, University of Erlangen, 91058 Erlangen, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Müller
authors.forename: Ingrid
authors.initials: I
authors.lastname: Obermeier
authors.forename: Miriam
authors.initials: M
authors.lastname: Wöhner
authors.forename: Carolin
authors.initials: C
authors.lastname: Brandl
authors.forename: Sarah
authors.initials: S
authors.lastname: Mrotzek
authors.forename: Sieglinde
authors.initials: S
authors.lastname: Angermüller
authors.forename: Palash C
authors.initials: PC
authors.lastname: Maity
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D020013:Calcium Signaling; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011485:Protein Binding; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000378:metabolism*
chemical_list: C497868:Cd22 protein, mouse; D008024:Ligands; D051918:Sialic Acid Binding Ig-like Lectin 2
keywords: B-lymphocyte differentiation; B-lymphocyte signaling; Siglecs