title: Surrogate light chain expression beyond the pre-B cell stage promotes tolerance in a dose-dependent fashion.
abstract: While surrogate light chain (SLC) expression is normally terminated in differentiating pre-B cells, co-expression of SLC and conventional light chains has been reported in a small population of autoreactive peripheral human B cells that accumulate in arthritic joints. Despite this association with autoimmunity the contribution of SLC expressing mature B cells to disease development is still unknown. We studied the pathogenicity of SLC(+) B cells in a panel of mice that transgenically express the SLC components VpreB and λ5 throughout B cell development. Here we report that although VpreB or λ5 expression mildly activated mature B cells, only moderate VpreB expression levels - in the absence of λ5 - enhanced IgG plasma cell formation. However, no autoantibody production was detectable in VpreB or λ5 transgenic mice and VpreB expression could not accelerate autoimmunity. Instead, moderate VpreB expression partially protected mice from induced autoimmune arthritis. In support of a tolerogenic role of SLC-transgenic B cells, we observed that in a dose-dependent manner SLC expression beyond the pre-B cell stage enhanced clonal deletion among immature and transitional B cells and rendered mature B cells anergic. These findings suggest that SLC expression does not propagate autoimmunity, but instead may impose tolerance.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Laurens P
authors.initials: LP
authors.lastname: Kil
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands; Department of Rheumatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Odilia B J
authors.initials: OB
authors.lastname: Corneth
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Marjolein J W
authors.initials: MJ
authors.lastname: de Bruijn
authors.affiliation: Department of Rheumatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Asmawidjaja
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands; Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs-University and Max-Planck-Institute for Immunobiology, Freiburg, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Krause
authors.affiliation: Department of Rheumatology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Lubberts
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Pieter Fokko
authors.initials: PF
authors.lastname: van Loo
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands. Electronic address: r.hendriks@erasmusmc.nl.
authors.forename: Rudi W
authors.initials: RW
authors.lastname: Hendriks
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology*; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA / Q000379:methods
chemical_list: D054444:Immunoglobulin Light Chains, Surrogate; D012333:RNA, Messenger
keywords: B cell receptor signaling; B cells; Pre-B cell receptor; Rheumatoid arthritis; Surrogate light chain; Transgenic mice