title: CD19 and CD22 regulate a B lymphocyte signal transduction pathway that contributes to autoimmunity.
abstract: The fate of B lymphocytes is dependent on intrinsic and B cell antigen receptor (BCR)-induced signals. These signals are modified and interpreted by other cell-surface molecules such as CD19 and CD22 that govern mature B cell activation. This review assesses our current understanding of how CD19 and CD22 regulate B lymphocyte signaling and how alterations in these response-regulators contribute to autoimmunity in mice and humans. We propose that CD19 functions as a specialized adapter protein that regulates B lymphocyte signaling and autoantibody production. Overexpression of CD19 by B cells in systemic sclerosis patients correlates with autoantibody production and transgenic mice that overexpress CD19 produce similar autoantibodies. CD19 establishes a novel Src-family kinase activation loop that regulates basal signal transduction thresholds in resting B cells and amplifies Src-family kinase activation following BCR ligation. Reciprocally, CD22 is a potent regulator of CD19 function. These observations provide insight into how CD19 and CD22 govern the molecular ordering and intensity of signals transduced in B cells that may contribute to autoimmunity.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC, USA. thomas.tedder@duke.edu
authors.forename: T F
authors.initials: TF
authors.lastname: Tedder
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: J C
authors.initials: JC
authors.lastname: Poe
authors.forename: M
authors.initials: M
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015815:Cell Adhesion Molecules; D006801:Humans; D037102:Lectins; D051379:Mice; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases