title: CD19 signaling pathways play a major role for murine AIDS induction and progression.
abstract: Infection of genetically susceptible mice with the LP-BM5 mixture of murine leukemia viruses including an etiologic defective virus (BM5def) causes an immunodeficiency syndrome called murine AIDS (MAIDS). The disease is characterized by interactions between B cells and CD4(+) T cells resulting in polyclonal activation of both cell types. It is known that BM5def is expressed at highest levels in B cells and that B cells serve as viral APC. The CD19-CD21 complex and CD22 on the surface of B cells play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival. CD19 integrates positive signals induced by B cell receptor ligation by interacting with the protooncogene Vav, which leads to subsequent tyrosine phosphorylation of this molecule. In contrast, CD22 negatively regulates Vav phosphorylation. To analyze the role of CD19, CD21, Vav, and CD22 in MAIDS, we infected mice deficient in CD19, CD21 (CR2), Vav-1, or CD22 with LP-BM5 murine leukemia viruses. Infected CR2(-/-) mice developed MAIDS with a time course and severity indistinguishable from that of wild-type mice. In contrast, CD19 as well as Vav-1 deficiency restricted viral replication and suppressed the development of typical signs of MAIDS including splenomegaly, lymphadenopathy, and hypergammaglobulinemia. Finally, CD22 deficiency was found to accelerate MAIDS development. These results provide novel insights into the B cell signaling pathways required for normal induction and progression of MAIDS.
authors.affiliation: Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Rockville, MD 20852, USA.
authors.forename: Sonja M
authors.initials: SM
authors.lastname: Knoetig
authors.forename: Ted A
authors.initials: TA
authors.lastname: Torrey
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Naghashfar
authors.forename: Tom
authors.initials: T
authors.lastname: McCarty
authors.forename: Herbert C
authors.initials: HC
authors.lastname: Morse
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D018941:Antigens, CD19 / Q000235:genetics / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D000998:Antiviral Agents / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D002461:Cell Line, Transformed; D018450:Disease Progression; D007106:Immune Sera / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis; D016130:Immunophenotyping; D037102:Lectins / Q000172:deficiency / Q000235:genetics; D009052:Leukemia Virus, Murine / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016183:Murine Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051567:Proto-Oncogene Proteins c-vav; D017464:Receptors, Complement 3d / Q000172:deficiency / Q000235:genetics; D012720:Severity of Illness Index; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016662:Virus Integration / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D000998:Antiviral Agents; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D007106:Immune Sera; D037102:Lectins; D011518:Proto-Oncogene Proteins; D051567:Proto-Oncogene Proteins c-vav; D017464:Receptors, Complement 3d; D051918:Sialic Acid Binding Ig-like Lectin 2; C496619:Vav1 protein, mouse; D007073:Immunoglobulin E