Light Chain Usage in Anti–double-stranded DNA B Cell Subsets: Role in Cell Fate Determination

作者：Linda Ann Spatz, Vladimir Saenko, Andrey Iliev, Lori A. Jones, Larisa J. Geskin, Betty Diamond · 发表于：The Journal of Experimental Medicine · 年份：1997 · DOI：10.1084/jem.185.7.1317 · 被引用次数：69 · 研究领域：Monoclonal and Polyclonal Antibodies Research、T-cell and B-cell Immunology、Immune Cell Function and Interaction

Two major mechanisms for the regulation of autoreactive B cells that arise in the bone marrow are functional silencing (anergy) and deletion. Studies to date suggest that low avidity interactions between B cells and autoantigen lead to B cell silencing, whereas high avidity interactions lead to deletion. Anti-double stranded (ds) DNA antibodies represent a pathogenic autospecificity in Systemic Lupus Erythematosus (SLE). An understanding of their regulation is critical to an understanding of SLE. We now demonstrate in a transgenic model in which mice express the heavy chain of a potentially pathogenic anti-DNA antibody that antibody affinity for dsDNA does not alone determine the fate of anti-dsDNA B cells. B cells making antibodies with similar affinities for dsDNA are regulated differently, depending on light chain usage. A major implication of this observation is that dsDNA may not be the self antigen responsible for cell fate determinations of anti-dsDNA B cells. Light chain usage may determine antigenic cross-reactivity, and cross-reactive antigens may regulate B cells that also bind dsDNA.