International Immunology Advance Access originally published online on May 17, 2004
International Immunology 2004 16(7):905-913; doi:10.1093/intimm/dxh092
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International Immunology, Vol. 16, No. 7, pp. 905-913,
July 2004
© 2004 Japanese Society for Immunology
Generation and selection of an IgG-driven autoimmune repertoire during B-lymphopoiesis in Igµ-deficient/lpr mice
Department of Immunology, Bruce Rappaport Faculty of Medicine and 1 Rappaport Family Institute for Research in the Medical Sciences, Technion-Israel Institute of Technology, Haifa, Israel
Correspondence to: D. Melamed; E-mail: melamedd{at}techunix.technion.ac.il
Transmitting editor: D. Wallach
Class switch recombination (CSR) is a well-regulated process that occurs in peripheral lymphoid tissue, and is thought of as an important factor constructing the memory repertoire. We have recently shown that CSR normally occurs during bone marrow (BM) development, and these isotype-switched B cells are negatively selected by Fas signaling. This novel pathway of B cell development may generate a primary repertoire driven by 
-heavy receptors, the nature of which is yet unknown. To study this H-driven repertoire we used mice lacking IgM-transmembrane tail exon (µMT), where B cell development is limited by their ability to undergo CSR. We already showed that lack of Fas signaling rescues development of a significant population of isotype-switched B cells and production of high titers of non-IgM serum antibodies in µMT mice deficient in Fas (µMT/lpr), thereby providing a mouse model allowing the assessment of H-driven repertoire. Using a tissue array and phage display epitope library we report here that IgG repertoire in µMT/lpr mice is oligo-monoclonal, bearing self-tissue reactivity. This is supported by analysis of the V
utilization in peripheral B cells from µMT/lpr mice, which revealed a strikingly restricted repertoire. In contrast, µMT/lpr B cells that are grown in non-selective BM cultures utilize a wide repertoire. These results suggest that the Fas pathway is an important regulator in the generation and selection of an autoimmune H-driven repertoire in vivo.
Keywords: antibodies, autoimmunity, B lymphocytes, hematopoiesis, repertoire development
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