HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by William, J. Articles by Shlomchik, M. J. Search for Related Content PubMed PubMed Citation Articles by William, J. Articles by Shlomchik, M. J. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Autoimmune Diseases

Visualizing the Onset and Evolution of an Autoantibody Response in Systemic Autoimmunity¹

Jacqueline William^*, Chad Euler^*, Elizabeth Leadbetter, Ann Marshak-Rothstein and Mark J. Shlomchik^2,*

^* Section of Immunobiology and Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520; and Department of Microbiology, Boston University School of Medicine, Boston, MA 02118

The onset of systemic autoimmunity is variable, making it difficult to identify early events. In this study, we show in rheumatoid factor (RF) Ig-transgenic autoimmune-prone mice that the appearance of RF B cells in blood signifies the onset of RF B cell activation in spleen, providing a novel window into the initiation of an autoantibody response. This allowed us to study the early and late phases of spontaneous induction of the B cell autoimmune response. Using this approach we showed that extensive Ab-forming cell generation in spleen, accompanied by somatic hypermutation, occurred despite the lack of an early germinal center response. The onset of the RF response correlated with the levels of IgG2a-containing immune complexes but not total IgG2a. By identifying the time of onset in individual mice, we were able to track progression of disease. We found remissions of RF Ab-forming cell production in some mice, suggesting that at the clonal level, chronic autoantibody responses are dynamic and episodic, much like acute pathogen responses. Surprisingly, there was little accumulation of long-lived plasma cells in bone marrow of mice with long-standing RF responses in spleen. These studies are among the first to define the early events of a spontaneous B cell autoimmune response.

This article has been cited by other articles:

				A. Lartigue, N. Colliou, S. Calbo, A. Francois, S. Jacquot, C. Arnoult, F. Tron, D. Gilbert, and P. Musette Critical Role of TLR2 and TLR4 in Autoantibody Production and Glomerulonephritis in lpr Mutation-Induced Mouse Lupus J. Immunol., November 15, 2009; 183(10): 6207 - 6216. [Abstract] [Full Text] [PDF]

				J. M. Odegard, B. R. Marks, L. D. DiPlacido, A. C. Poholek, D. H. Kono, C. Dong, R. A. Flavell, and J. Craft ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity J. Exp. Med., November 24, 2008; 205(12): 2873 - 2886. [Abstract] [Full Text] [PDF]

				J. William, C. Euler, N. Primarolo, and M. J. Shlomchik B Cell Tolerance Checkpoints That Restrict Pathways of Antigen-Driven Differentiation J. Immunol., February 15, 2006; 176(4): 2142 - 2151. [Abstract] [Full Text] [PDF]

				J. William, C. Euler, and M. J. Shlomchik Short-Lived Plasmablasts Dominate the Early Spontaneous Rheumatoid Factor Response: Differentiation Pathways, Hypermutating Cell Types, and Affinity Maturation Outside the Germinal Center J. Immunol., June 1, 2005; 174(11): 6879 - 6887. [Abstract] [Full Text] [PDF]