B lymphocytes of mice display an aberrant activation phenotype and are cell cycle arrested in G0/G1A during acute infection with Trypanosoma brucei.

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.