Third Eular Workshop on Rheumatology Research

Abstract

A chronic graft-versus-host reaction (GVHR) was induced in adult nonirradiated (B10 x DBA/2)F 1 mice by I.V. injection of live DBA/2 (H-2 d/d) lymphocytes. Although both a class I (K/D) and a class II (I-A/I-E) incompatibility existed in the F l recipients, DBA/2 donor cells were unable to induce the severe lympho-hemopoietic depletion characteristic of acute GVHD; in this DBA/2 differs from most other strains of mice, such as B10 and B6. Instead, DBA/2 cells induced an SLE-like GVHD which included the following symptoms: 1) autoantibodies to thymocytes, erythrocytes, nuclear antigens, dsDNA, and other less well-defined self-antigens ; 2) increased serum titers of antibodies to the surface antigen (gp70) of endogenous murine leukemia viruses; 3) a 10to 50-fold increase in spontaneous lgG formation and a 4-fold increase in IgM formation in the spleen, these were accompanied by hyper7-globulinemia; 4) a ubiquitous periarteritis; 5) the deposition of IgG and IgM antibodies along the basement membrane of the skin; and 6) a severe immune-complex glomerulonephritis ; significant amounts of anti-gp70 antibodies and antinuclear antibodies were eluted from diseased kidneys. In spite of the tremendous increase in spontaneous Ig production and the spontaneous formation of very high titers of SLE-like autoantibodies, however, we failed to detect a spontaneous formation of antibodies to non-self, such as SRBC, HRBC, TNP, levan, bacteriophage fd, and plasmodium berghei. Upon planned immunization with SRBC, the specific antibody response of SLE-like GVH mice was even decreased. Interestingly, there was no autoantibody formation to organ-specific antigens, such as thyroglobulin. Thus, the increased antibody formation in these SLE-like GVH mice was preferntiaUy, if not exclusively, directed against self-antigens involved in SLE. We propose that due to their intrinsic structure these self-antigens are more apt than others to trigger the corresponding autoreactive B cells in the presence of unspecific T cell help.

DOI: 10.1007/BF02032074

Cite this paper

@article{Gleichmann2005ThirdEW, title={Third Eular Workshop on Rheumatology Research}, author={Ernst Gleichmann and F. M. van Rappard-van der Veen and Anton G Rolink and Steven T. Pals and Gerhard Trautwein and M. Hewicker and John Douglas Waterfield and Ravinder N. Maini and Ulrich Botzenhardt and Jens M{\"{u}ller and E. -M. Lemmel and Rachael Bartlett and D. v. Steldern and Michelle Field and Leslie Schrieber and Richard D Melsom and P. J. W. Venables and Domenica A. McCarthy and Boukje de Vries and W. van den Berg and Levinus B. A. van de Putte and Jan Willem Lens and Marijn W. M. Kruijsen and Dieter Brackertz and Winfried Mohr and Rosemarie M Fritsch and Rikard Holmdahl and Katarina Rubin and Lars Klareskog and Th. Radaszkiewicz and Reiner Dreher and Gabriele J. Koehler and Peter Rieber and Ulrich Weber and Helga Kirchhoff and Jill Heitmann and Walter Hermanns and Laura C Schulz and Jeffrey C. Marquardt and P. Rojem and Stephanie Brighton and Wim A A Vermeulen and Rajneesh Madhok and Roger D. Sturrock and Charlie Forbes and D. W. Bennett and Wolfgang Leibold and Gaio Hangoc and Karl B{\"{o}hm and Matthaeus Rimpler and E. Grabczewska and Włodzimierz Maśliński and Krzysztof L Krzystyniak and J H Ryzewski and J. M. Mbuyi and Jan Dequeker and Peter Junker and Hans Oxlund and Gunnar Lorenzen and I B Lorenzen and Heidi Van Paassen and E. G. E. de Vries and Constant Mall{\'e}e and Olav L. M. Bijvoet and Annemieke Cats and John P. Ball and Dieter Wessinghage and C James Kirkpatrick and Gust Verbruggen and Frank Prosper Luyten and Eric M. Veys and Matthias Annefeld and M. Velvart and K L Fehr and Jorge Seidel and Heiner Menninger and Eric Gurr and Walter Stangel and Helmuth R. G. Deicher and C. Fobbe and Patrice Starck and Knut Kleesiek and Heidi Greiling and Pieter D. Biemond and A. J. G. Swaak and Johan F . Koster and Nick D. Hall and Cheryl L Maslen and Martin J. McKeown and Michael John Parnham and Christine Bittner and Nigel P Hurst and Bret F. Bessac and George Nuki and Josef Neumueller and Attila Dunky and G. Senautka and Robert Eberl and E. M. Lemmel and Jan {\AA}ke Lindgren and Thierry Appelboom and Robert Gortz and W J Madia and M . Binder . H . . Loos and H. P. Heinz and S. M. Mortazavi-Milani and E. J. Holborow and Sandra Lindblad and Eva Hedfors and C. J. L. M. Meijer and G. J. M. Lafeber and J. Vulpen-Cnossen and W. G. M. Damsteeg and Hans J{\"{o}rg Warnatz and Guenther Lemm and J. P. van der Weij and C. J. P. van der Veen and G. R. Burmester and Dirk Menche and Priscilla Merryman and Alexandra Dimitriu-Bona and Moti Klein and Robert J. Winchester and Charlie F Corke and V F Gul and H. E. Stierle and Edward C Huskisson and E. J. Holborrow and Karin S. Froebel and Rebecca Dickson and Deri Lewis and M{\'a}ria K{\'a}vai and I. Sonkoly and J{\'o}zsef Csongor and Gy. Szegedi and R. E. Schmidt and Eva Mollenhauer and Marion Heinrichs and Ch. Rittner and Elisabeth Marion Schneider and Graham Pawelec and Chr. M{\"{u}ller and Markus Blaurock and Sidney George Shaw and Peter Wernet and Vivienne R Winrow and Jacob Norton and Robert March and Roxana Santana and K. H. Deycke and Bettina Baruth and E. Weibbarth and Herv{\'e} G. Zeller and Alan Ebringer and Nicole Geissler and Staffan Hildebrand and Andrea Kemper and Erwin Krapf and D. R. Michiel Renger and Ingolf Schedel and Henning K Zeidler and H . H . Mielke and P. B. Krauledat and Friedel Krapf and Siegfried Baudner and H. Linhart and J. R. Kalden and PJ. Maddison and R. P. Skinner and Eva Esscher and Pamela V. Taylor and Ori Scott and Jackie S Scott and Pierre Miossec and Prof. P. Youinou and Philip Goff and Jean Marie Seigneurin and R. Coatalem and Freya Trautmann and Wolfgang Arnold and Ph. Hermanns and Jons Delanghe and Maarten Vansteenkiste and Herman Mielants and Eimar Munthe and E. J. Jellum and S. Suykens and Hilmar Schiller and F. Schilling and Eike Emrich}, journal={Clinical Rheumatology}, year={2005}, volume={2}, pages={81-106} }