Parasite infection causes marked perturbations in the host immune system, as shown by hypergammaglobulinemia, autoimmunity and immune depression, but there is little information on the number, specificities and performance of B cell clones activated in the course of infection. We have addressed these questions in a model of murine malaria induced by Plasmodium chabaudi, where primary infection results in very marked B cell responses that shift in Ig isotype pattern in immunoprotected animals, and where immunity can be transferred to naive recipients by injection of serum from late, but not early, infection. We have quantitated B cells responding to infection in two distinct functional compartments, namely blast cells and Ig-secreting cells, and compared normal with immune animals. We have also determined the frequencies of clonal specificities towards several autoantigens (DNA, myosin, transferrin and red cells), non-self protein or polysaccharide antigens (KLH, levan and dextran), and parasite antigens in both compartments, by measuring blast cell reactivities in limiting dilution analyses and Ig secretion in ELISASPOT assays. This experimental design allowed us to assess the specificity of the B cell responses, to compare the clonal composition of these two B cell compartments, and to evaluate putative specific response regulation at the step of terminal differentiation. Our results show that, in this particular experimental system: (i) B cell responses in primary infection are truly non-specific while immune animals show a greater ability to control the massive non-specific response; (ii) parasite specific B cells, particularly those committed to IgG production, are selectively stimulated in immune individuals; (iii) autoreactive B cells are not selectively stimulated, but increased autoantibody production may result from perturbation in the control of terminal differentiation in the respective clones; (iv) clones with specificity to some non-self antigens (e.g. KLH and dextran) are selectively engaged and regulated, which might have implications for the immunosuppression following infection.
Abstract The primary infection by P. chabaudi induces an increase of the numbers of splenic immunoglobulin (Ig)‐secreting B cells in both athymic and euthymic BALB/c mice. The isotypic pattern of the polyclonal response is restricted only in euthymic mice where IgG 2a , IgG 2b and IgM plaque‐forming cells (PFC) predominate. In immunized animals, protected against a parasite challenge, the isotypic pattern of splenic PFC is completely different, the IgG 1 and IgM isotypes constituting the main part of the response. Reinoculation of immune‐protected animals induces a PFC response which is dose dependent and accentuates the characteristic isotypic profile of the immune‐protected mice.
The molecular karyotypes of P. chabaudi and P. falciparum have been compared by pulse field gradient electrophoresis. P. chabaudi has 3 extra chromosomes in the 750-2000 Kb range although the overall number appears to be 14 as is the case for P. falciparum. The chromosomal location of the rRNA genes has been determined for P. chabaudi together with that of a 24 Kd antigen gene. The corresponding cDNA 443 may code for a protein unusually rich in tyrosine and contains sequences highly repetitive in P. falciparum.
Dans le modele experimental d'infection de la souris balb/c par plasmodium chabaudi, nous avons analyse le developpement de la reponse immunitaire protectrice, les effecteurs de l'immunite et les modifications de l'homeostasie du systeme immunitaire induites par l'infection. Pour induire une reponse immunitaire protectrice, nous avons utilise plusieurs protocoles: une infection suivie d'une cure chimio-therapeutique, une immunisation avec des extraits de parasites erythrocytaires, prepares a differents stades de developpement, le transfert passif de serum immun, la transfusion de globules rouges normaux. Tous les animaux ont developpe une infection aigue apres injection de parasites. La reponse immunitaire protectrice definie par la capacite de controler la croissance des parasites est declenchee une fois que les reticulocytes infectes ont atteint un seuil de densite, suggerant qu'ils pourraient etre l'immunogene vaccinant. Aucune difference n'est observee entre les animaux qui guerissent de l'infection et ceux qui meurent. L'immunite est sterile et specifique de la souche. La capacite a neutraliser rapidement une dose d'epreuve diminue au cours du temps ; mais les animaux, apres une infection marginale, retrouvent rapidement cette capacite. Les anticorps igg jouent un role majeur dans la destruction des parasites en conjonction avec des cellules radio-resistantes, presentes egalement chez l'animal naif transfuse, probablement des macrophages residents. La qualite des igg immunes, definie par leur capacite chez l'animal transfuse a retarder la croissance parasitaire d'une dose d'epreuve, depend de plusieurs parametres: le temps ecoule entre la dose d'epreuve delivree au donneur immun et la collecte de son serum, le nombre de parasites utilises dans la dose d'epreuve delivree au donneur de serum immun. Une activation polyclonale tres forte est observee au cours d'une infection primaire. La distribution des isotypes est differente dans l'infection aigue ou les igm, ig2a et igg2b dominent et, chez l'animal protege, ou les igm et igg1 representent la majorite de la reponse. En conclusion, nos donnees soulignent la complexite des mecanismes, de la reponse immunitaire et, de la destruction des parasites du paludisme
'/%3e%3cpath d='m450 224.315-44.467 136.87 116.401-84.559h-143.87l116.403 84.559z' style='fill:none;stroke:%23006233;stroke-width:14.62993431;stroke-miterlimit:4;stroke-dasharray:none'/%3e%3c/svg%3e)