CD4+ T cells play a major role for IgM and IgG anti-DNA production in mice infected with Plasmodium yoelii.
The infection by a non-lethal strain of Plasmodium yoelii induces the formation of autoantibodies such as anti-DNA and anti-Sm antibodies in mice. The extent of the relative increase in serum levels of IgM and IgG anti-DNA and anti-Sm antibodies and their kinetics were found to be similar to those of anti-hapten antibodies and of total IgM and IgG levels. This strongly suggested that anti-DNA and anti-Sm autoantibody responses observed in malaria-infected mice are a result of polyclonal activation of B cells. The analysis of the IgG subclasses reacting with DNA antigen showed significant levels of the T cell-dependent isotypes, IgG1 and IgG2. The role of T cells in the activation of autoreactive B cells was confirmed by using athymic nude mice. Indeed, BALB/c-nu/nu and C57BL/6-nu/nu mice failed to produce IgG anti-DNA antibodies after infection with P. yoelii. Moreover, the reconstitution of BALB/c nude mice with lymph node cells from congenic euthymic BALB-Igb mice showed the activation of autoreactive B cells in nude mice by T cells from euthymic mice. Studies in mice depleted of CD4+ T cells strongly suggested that malaria-induced anti-DNA antibodies were almost entirely dependent on the presence of CD4+ T cells, as this depletion significantly decreased IgM anti-DNA antibodies and completely abolished the IgG anti-DNA production, including the IgG3 subclass in infected mice. In contrast, depletion of the CD8+ T cell subset had no effect on the production of autoantibody in malaria-infected mice. Our results indicate that CD4+ T cells play a major role for both IgM and IgG anti-DNA production during the course of malaria infection.
Fossati
L
L
Department of Pathology, University of Geneva, Switzerland.
Merino
J
J
Izui
S
S
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010967:Plasmodium yoelii / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D000913:Antibodies, Protozoan; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins