title: CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms.
abstract: The interaction of CD22 with alpha2,6-linked sialic acid ligands has been widely proposed to regulate B lymphocyte function and migration. Here, we generated gene-targeted mice that express mutant CD22 molecules that do not interact with these ligands. CD22 ligand binding regulated the expression of cell surface CD22, immunoglobulin M and major histocompatibility complex class II on mature B cells, maintenance of the marginal zone B cell population, optimal B cell antigen receptor-induced proliferation, and B cell turnover rates. However, CD22 negative regulation of calcium mobilization after B cell antigen receptor ligation, CD22 phosphorylation, recruitment of SHP-1 to CD22 and B cell migration did not require CD22 ligand engagement. These observations resolve longstanding questions regarding the physiological importance of CD22 ligand binding in the regulation of B cell function in vivo.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Poe
authors.forename: Yoko
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Karen M
authors.initials: KM
authors.lastname: Haas
authors.forename: Ann S
authors.initials: AS
authors.lastname: Miller
authors.forename: Isaac G
authors.initials: IG
authors.lastname: Sanford
authors.forename: Cheryl B
authors.initials: CB
authors.lastname: Bock
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Tedder
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002465:Cell Movement; D037102:Lectins / Q000502:physiology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D051918:Sialic Acid Binding Ig-like Lectin 2
chemical_list: D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D019158:N-Acetylneuraminic Acid