Light chain usage in anti-double-stranded DNA B cell subsets: role in cell fate determination.
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.
Spatz
L
L
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Saenko
V
V
Iliev
A
A
Jones
L
L
Geskin
L
L
Diamond
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D000918:Antibody Specificity; D015551:Autoimmunity; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001483:Base Sequence; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology*; D007678:Kidney Glomerulus / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D004247:DNA