Scand. J. Immunol. 28, 553-561, 1988 Most B Cells in Acute Trypanosoma cruzi Infection Lack Parasite Specificity p. MINOPRIO, O. BURLEN, P. PEREIRA, B. GUILBERT, L. ANDRADE, IVI. HONTEBEYRIE-JOSKOWICZ & A. COUTINHO Department of Immunology, Pasteur Institute, Paris, France Minopdo, P,, Burlen, C, Pereira, P,, Guilbert, B,, Andrale, L,, Hontebeyrie-Joskowicz, M, & Coutinho, A, Most B Cells in Acute Trypanosoma cruzi Infection Lack Parasite Specificity, Scand. J. Immunol. 28, 553-561, 1988 The specificity of B lymphocytes activated in the acute phase of murine Trypanosoma cruzi infection was analysed in a panel of immunoglobulin-secreting hybridomas derived by fusion of lymph node cells 7 days after intraperitoneal parasite inoculation. The immunoglobulin isotype distribution of the hybrids reflected the total plaque-forming cell (PFC) response in the animal at this point, with a predominance of IgG2a, IgM, and IgG2b, Screening of the hybridoma antibodies on parasite antigens by three independent methods (western blot, ELISA, and immunofluorescence) revealed oniy one (out of a total of 51) that bound a parasite molecule with an apparent molecular mass of 180 kDa, In contrast, antibodies of both IgM and IgG classes were found to react with a panel of autologous antigens. These results establish that most B cells activated by T. cruzi infection are not specific for parasite antigens and therefore indicate the relevance of analysing the totality of host responses to infection, Paola Minoprio, Unite d'Immunoparasitologie, Institut Pasteur, 28, Rue du Dr Roux, Paris CEDEX15, France Experimental infection with parasitic protozoa leads to large increases in the number of immunoglobuhn (Ig)-secreting plasma cells in the spleen and lymph nodes [6, 8, 19], Human chronic infection is also characterized by hyper- gammaglobulinaemia [2,17,27], Such responses are often described as polyclonal and claimed to be antigen-nonspecific [4, 7, 23], In view of the extreme antigenic complexity of parasites, however, others have argued that the host response represents a specific immune activa- tion of lymphocyte clones directed against each of the many parasite determinants [9,17, 30, 31, 34], This problem is important because, if tbe abundant host response is for the most part para- site-specific, the next question should address the resistance of the parasite to antibody-depen- dent effector mechanisms. In contrast, if the host reaction to infection is largely nonspecific, the important questions concern the mecha- nisms of such reaction and its relevance in the auto-immunity and immunosuppression associ- ated with infection [14, 15, 24-26, 33], Further- more, attempts to increase host resistance should then be directed to the suppression of this host response, possibly by channelling it to a specific response. We have now directly addressed the question of parasite-specific versus non-specific immune response in a murine model of Trypanosoma cruzi infection, in which we had previously characterized some variables of the host responses [20-22], We derived a panel of Ig-secreting hybridomas by fusing lymph node cells directly recovered from acutely infected animals, and examined the range of specific reactivities of the corresponding monoclonal antibodies. The results show that all but one of the hybrids displayed no reactivity with T. cruzi antigens or extracts thereof. MATERIALS AND METHODS Mice. Eight-week-old male C57BL/6 mice bred at the Pasteur Institute were used. Parasites. The CL strain of T. cruzi [3] was main- tained as described [21], Animals were injected intra- 553