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Biomedical subjects

M Lemeur

Publications and source records attributed to M Lemeur.

6 recordsLinked to original sources
PubMed1998

Contributions of Ea(z) and Eb(z) MHC genes to lupus susceptibility in New Zealand mice.

Unlike parental New Zealand Black (NZB) or New Zealand White (NZW) mice, (NZB x NZW)F1 mice exhibit a lupus-like disease characterized by IgG autoantibody production and severe immune complex-mediated nephritis. In studies of the genetic susceptibility to disease in this F1 model, the NZW MHC (H2z) has been strongly linked with the development of disease, and it was hypothesized that class II MHC genes, particularly Ez genes, may underlie this genetic contribution. In the present study, we bred transgenic B6 mice expressing I-Ez or congenic B6 mice carrying H2z with NZB mice and used a backcross analysis to test the hypothesis that Ea(z) and/or Eb(z) genes account for the effect of H2z on disease. The genetic analysis of different backcross combinations showed that unlike mice carrying H2z, mice inheriting Ez transgenes do not demonstrate increased IgG autoantibody production or increased incidence of nephritis. Surprisingly, in the same transgenic backcross mice, inheritance of the endogenous H2b from the B6 strain was strongly linked with the production of IgG autoantibodies, but not with disease. Additional experiments suggested that the level of IgG3 autoantibody production, which is controlled by H2, may be important in the pathogenesis of renal disease. Contributions to autoantibody production were also detected from an NZB locus on distal chromosome 1 (previously named Nba2). Together, these studies provide new insight into the role of MHC in lupus-like autoimmunity.

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PubMed1993

Mice lacking TdT: mature animals with an immature lymphocyte repertoire.

In adult animals, template-independent (or N) nucleotides are frequently added during the rearrangement of variable (V), diversity (D), and joining (J) segments of lymphocyte receptor genes, greatly enhancing junctional diversity. Receptor genes from adult mice carrying a mutation in the terminal deoxynucleotidyl transferase (TdT) gene have few N nucleotides, providing proof that this enzyme is essential for creating diversity. Unlike those from normal adults, receptor genes from adult mutant mice show extensive evidence of homology-directed recombination, suggesting that TdT blocks this process. Thus, switch-on of the TdT gene during the first week after birth provokes an even greater expansion of lymphocyte receptor diversity than had previously been thought.

Animals↗
PubMed1993

Mice lacking the MHC class II-associated invariant chain.

The invariant chain (li) has aroused much interest because of its close association with major histocompatibility complex (MHC) class II molecules. Various functions have been proposed for it; several of these have received experimental support, but most have not been definitively proven, owing largely to uncertainties inherent in the experimental systems employed. We have now generated a line of mice devoid of the invariant chain by introducing a drastic mutation into the li gene. Cells from mutant animals show aberrant transport of MHC class II molecules, resulting in reduced levels of class II complexes at the surface, and these do not have the typical compact conformation indicative of tight peptide binding. Consequently, mutant cells present protein antigens very poorly and mutant mice are deficient in producing and at negatively selecting CD4+ T cells.

Animals↗
PubMed1991

Mice lacking MHC class II molecules.

We have produced mice that lack major histocompatibility complex class II antigens, permitting us to evaluate the role of these molecules in diverse aspects of T and B cell differentiation. The mutant mice show near-complete elimination of CD4+ T lymphocytes from the spleen and lymph nodes; the few remaining CD4-positive cells are preferentially localized to B cell follicles. Surprisingly, substantial numbers of CD4 single-positive cells reside in the thymus; however, these are not mature thymocytes as we currently recognize them. B lymphocytes occur in normal numbers and are capable of terminal differentiation to plasma cells. Nevertheless, several aberrations in the B cell compartment are demonstrable: a lack of germinal centers, fewer IgM+IgD+ cells in certain individuals, reduced production of serum IgG1, and complete inability to respond to T-dependent antigens. In short, the class II-negative mice have confirmed some old ideas about lymphocyte differentiation, but have provided some surprises.

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PubMed1989

Analysis of the HLA-Cw3-specific cytotoxic T lymphocyte response of HLA-B7 X human beta 2m double transgenic mice.

The cytolytic responses of either normal (non transgenic), HLA-B7 (single transgenic) or HLA-B7 x human beta 2 microglobulin (double transgenic) DBA/2 mice induced by transfected HLA-Cw3 P815 (H-2d) mouse mastocytoma cells were compared, to evaluate whether the expression of an HLA class I molecule in responder mice would favor the emergence of HLA-specific, H-2-unrestricted CTL. Only 8 of 300 HLA-Cw3-specific CTL clones tested could selectively lyse HLA-Cw3-transfected cells in an H-2-unrestricted manner, all having been isolated after hyperimmunization of double transgenic mice. These clones also lysed HLA-Cw3+ human cells. Unexpectedly, the lysis of the human but not that of the murine HLA-Cw3 cells was inhibited by Ly-2,3-specific mAb. Despite significant expression of HLA-B7 class I molecules on transgenic lymphoid cells, including thymic cells, limiting dilution analysis and comparative study of TCR-alpha and -beta gene rearrangements of the eight isolated clones (which suggested that they all derived from the same CTL precursor) indicated that the frequency of HLA-Cw3-specific H-2 unrestricted cytotoxic T lymphocytes remained low (even in HLA-B7 x human beta 2-microglobulin double transgenic mice). This suggests that coexpression of HLA class I H and L chain in transgenic mice is not the only requirement for significant positive selection of HLA class I-restricted cytotoxic mouse T lymphocytes.

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