title: 2,4,6-trinitrophenyl (TNP) responsiveness of anti-TNP (Sp6) transgenic mice.
abstract: Transgenic mouse models have demonstrated clonal deletion as well as clonal anergy of monospecific, high-avidity autoreactive B cell. The function and fate of naturally activated B cells, many of them displaying degenerate specificity including autoreactivity, are still a matter of debate. The question was pursued in Sp6-transgenic mice. Sp6, a monoclonal anti-2,4,6-trinitrophenyl (TNP) IgM has been shown to react with a variety of self antigens. Responsiveness of antibody-secreting B cells was followed throughout postnatal development of Sp6-transgenic mice and was related to the availability of antigen- and idiotype-specific help. Thymus as well as spleen cells of transgenic mice contained a significantly higher number of TNP-specific B cell than non-transgenic controls. In contrast to control mice, the number of TNP-specific B cells remained unchanged or decreased in thymus and spleen of transgenic mice after antigenic stimulation with TNP in T-dependent (TD) and T-independent (TI) form. Since the relative frequency of transgenic B cells was in particular diminished after repeated stimulation with TD antigen, it was examined whether limited responsiveness was linked to the available repertoire of helper T cells. Early after birth of transgenic individuals, thymic as well as splenic T cells which proliferated in response to TNP and Sp6 and provided help for B cells were found to be significantly augmented. Their number decreased rapidly during postnatal maturation and Th cells did not expand after antigenic stimulation. There was no indication that in the naive host transgenic B cells would suppress proliferation of TNP- and Sp6-specific T cells, but they did so after antigenic stimulation. Furthermore, and in contrast to B cells of non-transgenic mice, transgenic B cells were unable to present nominal antigen in a stimulatory way. The decrease in the number of B cells after antigenic stimulation indicated that autoreactive transgenic B cells may be subject to (functional) deletion under selected circumstances. In addition, idiotype- and antigen-specific help was impaired in Sp6-transgenic mice and this clearly was due to interactions with B cells expressing the immunoglobulin transgene.
authors.affiliation: Institute of Radiology and Pathophysiology, German Cancer Research Center, Heidelberg.
authors.forename: M
authors.initials: M
authors.lastname: Zöller
mesh_terms: D000367:Age Factors; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D015536:Down-Regulation; D005803:Genes, Immunoglobulin; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*; D014301:Trinitrobenzenes / Q000276:immunology*
chemical_list: D014301:Trinitrobenzenes