Regulation of B cell development and B cell signalling by CD22 and its ligands alpha2,6-linked sialic acids.
CD22 is an inhibitory co-receptor of B cell receptor (BCR)-mediated signalling which binds specifically to glycan ligands containing alpha2,6-linked sialic acids. This interaction modulates the CD22 activity by an unknown mechanism. Mice deficient for ST6GalI, the enzyme that generates alpha2,6-linked sialic acids, show an immunodeficient and opposing phenotype to CD22-deficient mice. By generating mice double-deficient for this receptor/ligand pair, we analysed its influence on B cell maturation and signalling. Both ST6GalI-deficient and ST6GalI x CD22-deficient mice showed normal B cell development, but an impaired marginal zone B cell population in the spleen. Both types of mutant mice also showed a reduced population of bone marrow recirculating B cells, a defect previously detected in CD22-/- mice. In adoptive transfer experiments, a migration defect of wild-type B cells to the bone marrow of ST6GalI-deficient mice was found. This suggests a direct involvement of CD22 and its ligands 2,6Sia in a homing process of recirculating B cells to the bone marrow. Interestingly, defective B cell Ca2+ signalling and proliferation of ST6Gal-/- mice was rescued in ST6GalI x CD22-deficient mice. This points to a new mechanism of BCR signal regulation by CD22 and its ligand.
Department of Genetics, University of Erlangen, Erlangen, Germany.
Snigdha
S
Ghosh
Claudia
C
Bandulet
Lars
L
Nitschke
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D019158:N-Acetylneuraminic Acid / Q000172:deficiency / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D012799:Sialyltransferases / Q000172:deficiency; D015398:Signal Transduction / Q000276:immunology*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase