title: Maintenance of anti-Sm/RNP autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory B cells.
abstract: Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, it is unclear whether it serves a functional role in autoimmune responses. 2,6,10,14-Tetramethylpentadecane causes chronic peritoneal inflammation and lupus-like disease with autoantibody production and ectopic lymphoid tissue (lipogranuloma) formation. A novel transplantation model was used to show that transplanted lipogranulomas retain their lymphoid structure over a prolonged period in the absence of chronic peritoneal inflammation. Recipients of transplanted lipogranulomas produced anti-U1A autoantibodies derived exclusively from the donor, despite nearly complete repopulation of the transplanted lipogranulomas by host lymphocytes. The presence of ectopic lymphoid tissue alone was insufficient, as an anti-U1A response was not generated by the host in the absence of ongoing peritoneal inflammation. Donor-derived anti-U1A autoantibodies were produced for up to 2 mo by plasma cells/plasmablasts recruited to the ectopic lymphoid tissue by CXCR4. Although CD4(+) T cells were not required for autoantibody production from the transplanted lipogranulomas, de novo generation of anti-U1A plasma cells/plasmablasts was reduced following T cell depletion. Significantly, a population of memory B cells was identified in the bone marrow and spleen that did not produce anti-U1A autoantibodies unless stimulated by LPS to undergo terminal differentiation. We conclude that 2,6,10,14-tetramethylpentadecane promotes the T cell-dependent development of class-switched, autoreactive memory B cells and plasma cells/plasmablasts. The latter home to ectopic lymphoid tissue and continue to produce autoantibodies after transplantation and in the absence of peritoneal inflammation. However, peritoneal inflammation appears necessary to generate autoreactive B cells de novo.
authors.affiliation: Division of Rheumatology and Clinical Immunology, University of Florida, Gainesville, FL 32610-0221, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Delano
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Kindra M
authors.initials: KM
authors.lastname: Kelly-Scumpia
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Philip O
authors.initials: PO
authors.lastname: Scumpia
authors.forename: Lijun
authors.initials: L
authors.lastname: Yang
authors.forename: Eric
authors.initials: E
authors.lastname: Sobel
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002828:Choristoma / Q000276:immunology; D005260:Female; D006099:Granuloma / Q000097:blood / Q000276:immunology / Q000473:pathology; D007156:Immunologic Memory; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D017411:Ribonucleoproteins, Small Nuclear