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2,4,6‐Trinitrophenyl (TNP) responsiveness of anti‐TNP (Sp6) transgenic mice
Author(s) -
Zöller Morgot
Publication year - 1991
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.1830210705
Subject(s) - biology , transgene , genetically modified mouse , antigen , spleen , b cell , immunology , idiotype , t cell , naive b cell , stimulation , antibody , microbiology and biotechnology , immune system , monoclonal antibody , antigen presenting cell , endocrinology , gene , genetics
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 T h 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.