B cells are essential for vaccination-induced resistance to virulent Toxoplasma gondii.
T lymphocytes and gamma interferon (IFN-gamma) are known mediators of immune resistance to Toxoplasma gondii infection, but whether B cells also play an important role is not clear. We have investigated this issue using B-cell-deficient (muMT) mice. If vaccinated with attenuated T. gondii tachyzoites, muMT mice are susceptible to a challenge intraperitoneal infection with highly virulent tachyzoites that similarly vaccinated B-cell-sufficient mice resist. Susceptibility is evidenced by increased numbers of parasites at the challenge infection site and by extensive mortality. The susceptibility of B-cell-deficient mice does not appear to be caused by deficient T-cell functions or diminished capacity of vaccinated and challenged B-cell-deficient mice to produce IFN-gamma. Administration of Toxoplasma-immune serum, but not nonimmune serum, to vaccinated B-cell-deficient mice significantly prolongs their survival after challenge with virulent tachyzoites. Vaccinated mice lacking Fc receptors or the fifth component of complement resist a challenge infection, suggesting that neither Fc-receptor-dependent phagocytosis of antibody-coated tachyzoites nor antibody-dependent cellular cytotoxicity nor antibody-and-complement-dependent lysis of tachyzoites is a crucial mechanism of resistance. However, Toxoplasma-immune serum effectively inhibits the infection of host cells by tachyzoites in vitro. Together, the results support the hypothesis that B cells are required for vaccination-induced resistance to virulent tachyzoites in order to produce antibodies and that antibodies may function protectively in vivo by blocking infection of host cells by tachyzoites.
Sayles
P C
PC
Trudeau Institute, Inc., Saranac Lake, New York 12983, USA.
Gibson
G W
GW
Johnson
L L
LL
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D003182:Complement C5 / Q000502:physiology; D005260:Female; D007106:Immune Sera / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D011961:Receptors, Fc / Q000502:physiology; D014124:Toxoplasmosis, Animal / Q000276:immunology*; D014611:Vaccination; D014774:Virulence
D003182:Complement C5; D007106:Immune Sera; D011961:Receptors, Fc; D007371:Interferon-gamma