CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling

Müller J, Obermeier I, Wöhner M, Brandl C, Mrotzek SJ, Angermüller S, Maity PC, Reth M, Nitschke L (2013)

Publication Status: Published

Publication Type: Journal article

Publication year: 2013

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Publisher: NATL ACAD SCIENCES

Book Volume: 110

Pages Range: 12402-12407

Journal Issue: 30

DOI: 10.1073/pnas.1304888110

Abstract

A high proportion of human B cells carry B-cell receptors (BCRs) that are autoreactive. Inhibitory receptors such as CD22 can down-modulate autoreactive BCR responses. With its extracellular domain, CD22 binds to sialic acids in alpha 2,6 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 Ca2+ signaling by controlling the CD22 association to the BCR. Mice with a mutated CD22 ligand-binding domain of CD22 showed strongly reduced Ca2+ signaling. In contrast, mice with mutated CD22 immunoreceptor tyrosine-based inhibition motifs have increased B-cell Ca2+ 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 with CRIS profile

Miriam Wöhner Professur für Genetik Carolin Brandl Professur für Genetik Sarah Johanna Meyer Sonderforschungsbereich/Transregio 130 B-Zellen: Immunität und Autoimmunität Sieglinde Angermüller Lehrstuhl für Genetik Lars Nitschke Professur für Genetik

Involved external institutions

Albert-Ludwigs-Universität Freiburg DE Germany (DE)

How to cite

APA:

Müller, J., Obermeier, I., Wöhner, M., Brandl, C., Mrotzek, S.J., Angermüller, S.,... Nitschke, L. (2013). CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling. Proceedings of the National Academy of Sciences of the United States of America, 110(30), 12402-12407. https://dx.doi.org/10.1073/pnas.1304888110

MLA:

Müller, Jennifer, et al. "CD22 ligand-binding and signaling domains reciprocally regulate B-cell Ca2+ signaling." Proceedings of the National Academy of Sciences of the United States of America 110.30 (2013): 12402-12407.

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