Sialylated multivalent antigens engage CD22 in trans and inhibit B cell activation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 8; pp. 2500 - 2505
• Main Authors: Courtney, Adam H, Puffer, Erik B, Pontrello, Jason K, Yang, Zhi-Qiang, Kiessling, Laura L
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 24.02.2009; National Acad Sciences
• Subjects: Animals; Antigens; B lymphocytes; B-Lymphocytes - immunology; Biochemistry; Biological Sciences; Carbohydrate Sequence; Cell Line; Cells; Copolymers; Glycoconjugates; Glycoproteins; Humans; Immune system; Ligands; Lymphocyte Activation - immunology; Lymphocytes; Molecular Sequence Data; N-Acetylneuraminic Acid - chemistry; Phosphorylation; Physical Sciences; Physiological regulation; Polymers; Receptors; Sialic Acid Binding Ig-like Lectin 2 - chemistry; Sialic Acid Binding Ig-like Lectin 2 - immunology; Signal Transduction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0807207106

CD22 is an inhibitory coreceptor on the surface of B cells that attenuates B cell antigen receptor (BCR) signaling and, therefore, B cell activation. Elucidating the molecular mechanisms underlying the inhibitory activity of CD22 is complicated by the ubiquity of CD22 ligands. Although antigens can display CD22 ligands, the receptor is known to bind to sialylated glycoproteins on the cell surface. The propinquity of CD22 and cell-surface glycoprotein ligands has led to the conclusion that the inhibitory properties of the receptor are due to cis interactions. Here, we examine the functional consequences of trans interactions by employing sialylated multivalent antigens that can engage both CD22 and the BCR. Exposure of B cells to sialylated antigens results in the inhibition of key steps in BCR signaling. These results reveal that antigens bearing CD22 ligands are powerful suppressors of B cell activation. The ability of sialylated antigens to inhibit BCR signaling through trans CD22 interactions reveals a previously unrecognized role for the Siglec-family of receptors as modulators of immune signaling.