TRENDS in Immunology Vol.22 No.12 December 2001 http://immunology.trends.com 1471-4906/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S1471-4906(01)02052-X 653 Research Update Meeting Report In conjunction w ith the 11th International Congress of Immunology in Stockholm, Sweden, the satellite meeting on B cells and Autoimmunity: New Concepts and Therapeutic Perspectives was held in Bergen, Norway from 19–21 July 2001. The origin of autoimmune diseases remains enigmatic. For several years, attention was centered largely on the study of T cells. Over the past few years, however, there has been a revival of interest in the role of B cells in autoimmune diseases, with evidence from different studies showing that the pathogenesis of autoimmune diseases cannot be accounted for solely by the action of T cells 1–4 . The major goal of the organizers was to view and discuss recent advancements in our knowledge of B-cell biology that will aid in the understanding of autoimmunity. As the meeting progressed among the fjords of Norway, several major themes crystallized. Receptor editing and autoimmunity As one of the mechanisms involved in maintaining B-cell tolerance to self, receptor editing exploits the capacity of Ig variable-region (V) genes to undergo successive rearrangements, allowing B cells to avoid high-affinity autorecognition 5 . Hence, receptor editing has implications with regard to the maintenance of B-cell tolerance and, possibly, the induction of pathogenic autoimmunity. M. Nussenzweig (New York, NY, USA) has developed two mouse models, in which mice express one mouse κ locus and the human constant region Cκ locus, allowing direct examination of receptor editing by flow cytometry. The mouse B cells are targeted for editing during a two-hour delay in development at the pre-B-cell stage. As many as 25–33% of mature B cells exhibited evidence of receptor editing, implying that editing plays a major role in shaping the peripheral antibody repertoire. M. Weigert (Princeton, NJ, USA) discussed the role of various molecular mechanisms of receptor editing and/or revision in preventing the development of autoimmunity. In some circumstances, re-expression of a second light chain, without editing of the first light chain V region (V L ), might prevent the action of the ‘master editor’ (the light-chain gene product that prevents autoimmunity) and permit the re-emergence of specificities that bind to autoantigen. Weigert described the existence of B cells that express dual receptors in the marginal zone of lymph nodes, and suggested that restriction of these cells to this location might prevent them from developing into fully autoreactive B cells. It will be important to elucidate how these multireactive B cells might contribute to autoimmunity. In his studies of receptor editing in the MRL mouse model of lupus, M. Monestier (Philadelphia, PA, USA) found an increased frequency of diversity region (D–D) fusions and evidence of secondary heavy-chain (H) diversity and joining region (D–J H ) rearrangements in newborn autoimmune mice. This was not found in pre-B cells, suggesting that secondary V H gene rearrangements in the periphery of MRL mice might contribute to the emergence of autoimmunity. In humans, P. Lipsky (Bethesda, MD, USA) described the V H and V L repertoire in normal individuals compared with those suffering from autoimmunity. Evidence of marked B-cell hyperactivity was found in patients with lupus, including increased somatic mutation and receptor editing, and abnormal selection in the periphery. B-cell memory and homing Interest in the role of B-cell memory and the germinal-center reaction in autoimmunity is growing. C. Berek (Berlin, Germany) described the characteristics of the inflammatory foci that form at affected sites in rheumatoid arthritis (RA) patients. These foci comprise immunocompetent cells [follicular dendritic cells (FDCs) and B cells (Ki67 + CD79 + CD20 + CD38 + )] that form fully functional germinal centers. Proliferating B cells from synovial fluid exhibit evidence of somatic hypermutation in their V-region genes. In the peripheral blood of many RA patients, she found that an increased frequency of B cells with a memory phenotype (CD19 + CD27 + ) that are hypermutated. A population (up to 48%) of CD19 + CD27 high plasma cells was present also in the patients, a reflection of chronic activation. In Sjögren Syndrome, the data of J. Bohnhorst (Oslo, Norway) showed decreased numbers of CD27 + memory B cells in SS patients and increased levels of soluble CD27 in the serum. Studying salivary glands from primary SS patients, S. Bowman (Birmingham, UK) found that the expression of chemokines and chemokine receptors reflects the distribution of inflammatory cells in this tissue 6 . Stromal-cell-derived factor 1 (SDF-1) was expressed highly in ductal epithelial cells, and its ligand, CXC-chemokine receptor 4 (CXCR4), was expressed on periductal inflammatory cells. B-lymphocyte chemoattractant was expressed in a diffuse fashion, and its ligand, CXCR5, was expressed by a portion of B cells in structures resembling germinal centers. Animal models and genetic susceptibility In autoimmune research, geneticists are expending great efforts to identify the genes that might confer susceptibility. In humans, J.B. Harley (Oklahoma City, OK, USA) discussed linkage studies of human lupus in at least five centers in Europe and North America. The data are consistent with the ‘established’ linkages found at chromosomes 1q41, 2q37, 4p16, 6p21 and 16q13. In the mouse, A. Theofilopoulos (La Jolla, CA, USA) reported genome-wide mapping efforts to define loci for the lupus- prone mouse strains New Zealand Black (NZB), NZ white (NZW), lymphoproliferative MRL–Fas–lpr and BXSB. With this framework in place, identification of the specific genetic alterations and mechanisms is now proceeding through the generation of interval congenic lines, and precise mapping and screening of candidate genes. In an experimental model of arthritis, R. Holmdahl (Lund, Sweden) identified the major genetic regions involved using F2 crosses of different mouse strains. Two loci associated with arthritis were identified: one on chromosome 2, at the location of the B-lymphocyte selection and autoimmunity Roland Jonsson, Karl Albert Brokstad, Peter E. Lipsky and Moncef Zouali