CD4 + T cells play a major role for IgM and IgG anti‐DNA production in mice infected with Plasmodium yoelii

SUMMARY 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‐Ig b 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.