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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.

journal_name

Proc Natl Acad Sci U S A

journal_title

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

authors

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

doi

10.1073/pnas.1304888110

subject

Has Abstract

pub_date

2013-07-23 00:00:00

pages

12402-7

issue

30

eissn

0027-8424

issn

1091-6490

pii

1304888110

journal_volume

110

pub_type

杂志文章

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