Modulation of immune system function by measles virus infection. II. Infection of B cells leads to the production of a soluble factor that arrests uninfected B cells in G0/G1.
Measles can result in a variety of immunologic defects. Previously we showed that an Epstein-Barr virus-transformed B cell line (B cells), when infected with measles virus, produced a soluble antiproliferative factor that inhibited proliferation of T and B cells. Here we explore the effects of infection by measles virus versus the virus-free soluble antiproliferative factor on B cells. The B cells showed no change in the amounts of interleukin (IL)-2, 10, 12, interferon (IFN)-gamma, or transforming growth factor (TGF)-beta when infected or exposed to the soluble factor. Similarly, B cells showed no change in the expression of class II major histocompatibility antigens, LFA-1, ICAM-1, CD19, CD40, CD80, CD86, CD95 (Fas), or CD178 (FasL). Cell cycle analysis showed that measles virus infection caused an accumulation of cells in S and G(2)/M phases with a "sub-G(1)" cell population, while incubation of cells with the soluble factor caused an accumulation in G(0)/G(1). These experiments provide evidence that measles virus causes a profound inhibition of B cell proliferation without distinguishable changes in cytokine profile or cell surface phenotype. Further, it appears that there are two populations of cells affected by infection: one population is growth arrested due to the influence of the immunosuppressive factor and is not infected; a second population that is infected progresses through S phase less efficiently. Alternatively, while both the soluble factor and live virus infection may affect cells in G(0)/G(1) phases, only live virus infection could selectively induce apoptosis of G(0)/G(1) cells, resulting in cell accumulation in S and G(2)/M phases with a build up of "sub-G(1)" cells.
Division of Hematology/Oncology/Bone-Marrow Transplantation, The Children's Hospital Denver, Colorado, USA.
Michael
M
Wang
Jane E
JE
Libbey
Ikuo
I
Tsunoda
Robert S
RS
Fujinami
D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002461:Cell Line, Transformed; D017077:Culture Media, Conditioned; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008457:Measles / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D008459:Measles virus / Q000276:immunology / Q000472:pathogenicity*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D012995:Solubility
D017077:Culture Media, Conditioned; D007155:Immunologic Factors