title: B lymphocytes of mice display an aberrant activation phenotype and are cell cycle arrested in G0/G1A during acute infection with Trypanosoma brucei.
abstract: Humans and domestic animals with African trypanosomiasis exhibit abnormalities of immune function characterized by polyclonal lymphocyte activation and, paradoxically, progressive immunodeficiency. Mice infected with Trypanosoma brucei clone IaTat1.2 develop a fulminant parasitemia by day 5 of infection. B lymphocytes isolated from spleens of infected mice display an aberrant activation phenotype manifested by decreased CD23 and surface IgM, increased CD69 and L-selectin, and normal levels of surface IgD, MHC class II, CD32, and transferrin receptor. Kinetic analyses showed that CD23 and surface IgM were continuously down-regulated from day 2 through day 5, whereas MHC class II was elevated on days 2 and 3, but returned to normal levels by day 5, suggesting that CD23 and MHC class II are independently regulated in T. brucei infection. The aberrant activation phenotype of B cells responding in vivo to T. brucei was accompanied by impaired responsiveness of these B cells to mitogenic stimulation in vitro. The pathologic phenotypic and functional properties of B lymphocytes from T. brucei-infected mice can be partially accounted for by the virtual total arrest of B cells in G0/G1A of the cell cycle. The B lymphocyte alterations observed in the present studies provide new insight into the immunopathology of African trypanosomiasis. We propose that terminal infection with T. brucei induces early activation events in host B lymphocytes, but that the activation response becomes aberrant by the development of what seems to be a total block in cell cycle progression.
authors.affiliation: Department of Pathology, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: R E
authors.initials: RE
authors.lastname: Sacco
authors.forename: M
authors.initials: M
authors.lastname: Hagen
authors.forename: J E
authors.initials: JE
authors.lastname: Donelson
authors.forename: R G
authors.initials: RG
authors.lastname: Lynch
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002453:Cell Cycle; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D017455:Receptors, IgE / Q000032:analysis; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000276:immunology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D017493:Leukocyte Common Antigens; D011947:Receptors, Antigen, B-Cell; D017455:Receptors, IgE; D000099192:CD69 Antigens