B-LYMPHOCYTES OF MICE DISPLAY AN ABERRANT ACTIVATION PHENOTYPE AND ARE CELL-CYCLE ARRESTED IN G(0) G(1A) DURING ACUTE INFECTION WITH TRYPANOSOMA-BRUCEI/

Humans and domestic animals with African trypanosomiasis exhibit abnor malities of immune function characterized by polyclonal lymphocyte act ivation and, paradoxically, progressive immunodeficiency. Mice infecte d with Trypanosoma brucei clone laTat1.2 develop a fulminant parasitem ia by day 5 of infection. B lymphocytes isolated from spleens of infec ted mice display an aberrant activation phenotype manifested by decrea sed CD23 and surface IgM, increased CD69 and L-selectin, and normal le vels of surface IgD, MHC class II, CD32, and transferrin receptor. Kin etic 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 th at CD23 and MHC class II are independently regulated in T. brucei infe ction. The aberrant activation phenotype of B cells responding in vivo to T. brucei was accompanied by impaired responsiveness of these B ce lls to mitogenic stimulation in vitro. The pathologic phenotypic and f unctional properties of B lymphocytes from T. brucei-infected mice can be partially accounted for by the virtual total arrest of B cells in G(0)/G(1A) of the cell cycle. The B lymphocyte alterations observed in the present studies provide new insight into the immunopathology of A frican trypanosomiasis. We propose that terminal infection with T. bru cei induces early activation events in host B lymphocytes, but that th e activation response becomes aberrant by the development of what seem s to be a total block in cell cycle progression.