Ablation of CD22 in ligand-deficient mice restores B cell receptor signaling.
CD22 is a negative regulator of B cell signaling, an activity modulated by its interaction with glycan ligands containing alpha2-6-linked sialic acids. B cells deficient in the enzyme (ST6Gal I) that forms the CD22 ligand show suppressed BCR signaling. Here we report that mice deficient in both CD22 and its ligand (Cd22-/- St6gal1-/- mice) showed restored B cell receptor (BCR) signaling, suggesting that the suppressed signaling of St6gal1-/- cells is mediated through CD22. Coincident with suppressed BCR signaling, B cells lacking ST6Gal I showed a net redistribution of the BCR to clathrin-rich microdomains containing most of the CD22, resulting in a twofold increase in the localization of CD22 together with the BCR. These studies suggest an important function for the CD22-ligand interaction in regulating BCR signaling and microdomain localization.
Collins
Brian E
BE
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Smith
Brian A
BA
Bengtson
Per
P
Paulson
James C
JC
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D022163:Clathrin-Coated Vesicles / Q000276:immunology; D066298:In Vitro Techniques; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000235:genetics / Q000378:metabolism*; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
C497868:Cd22 protein, mouse; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase