Maintenance of anti-Sm/RNP autoantibody production by plasma cells residing in ectopic lymphoid tissue and bone marrow memory B cells

Jason S. Weinstein, Matthew J. Delano, Yuan Xu, Kindra M. Kelly-Scumpia, Dina C. Nacionales, Yi Li, Pui Y. Lee, Philip O. Scumpia, Lijun Yang, Eric Sobel, Lyle L. Moldawer, Westley H. Reeves

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Although ectopic lymphoid tissue formation is associated with many autoimmune diseases, itis 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.

Original languageEnglish (US)
Pages (from-to)3916-3927
Number of pages12
JournalJournal of Immunology
Volume190
Issue number8
DOIs
StatePublished - Apr 15 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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