Regulation of B cell responses to the variant surface glycoprotein molecule in trypanosomiasis. II. Down-regulation of idiotype expression is associated with the appearance of lymphocytes expressing antiidiotypic receptors

The current study examines the idiotypic expression and regulation of variant surface glycoprotein (VSG)-specific B cell responses during African trypanosomiasis. Utilizing competitive inhibition RIA analysis, we detected antibodies in the serum of BALB/cByJ mice infected with Trypanosoma brucei rhodesiense clone LouTat 1.5 that recognized the same VSG epitopes as three VSG 1.5-specific mAb. These epitope-specific antibody responses were detectable by day 5 of infection, peaked by day 10, and then declined slowly through day 15 of infection. VSG-specific antibodies detectable in the serum of infected BALB/cByJ mice included those that were idiotypically cross-reactive with the VSG 1.5-specific mAb. These idiotypically defined, VSG-specific antibody responses appeared to peak around day 7 of infection, but then declined to near preimmune levels by day 15 of infection, demonstrating that the aggregate epitope-specific response was composed only in part by the idiotypically cross-reactive responses. Although corresponding antiidiotypic antibodies could not be detected in infected sera during periods of up- or down-regulation of idiotypically defined antibodies, flow cytometry analysis of lymphocytes isolated from the spleens of LouTat 1.5-infected BALB/cByJ mice revealed the presence of antiidiotypic receptor-bearing cells. These cells were detectable primarily during days 10 to 12 of infection and subsequently down-regulated their receptors, or declined in numbers, to near preimmune levels by day 15 of infection. The appearance of these antiidiotypic receptor-bearing cells coincides with the decline of idiotypic antibody present in the serum of the LouTat 1.5-infected mice and may represent nascent evidence for idiotypic regulation of trypanosome-specific immune responses in infected animals.