Circulating human B cells that express surrogate light chains and edited receptors.
Immunoglobulin gene recombination can result in the assembly of self-reactive antibodies. Deletion, anergy or receptor editing normally silence B cells that produce these autoantibodies. Receptor editing is highly efficient in mouse B cells that carry pre-recombined autoantibody transgenes or gene "knock-ins". However, it has been difficult to identify cells that have edited receptors in unmanipulated mice and humans. To try to identify such cells we isolated and characterized B cells that coexpress surrogate and conventional light chains (V-preB+L+) from the blood of normal human donors. V-preB+L+ B cells express RAG mRNA, display an unusual heavy and light chain antibody repertoire consistent with antiself reactivity, and show evidence of receptor editing. These cells accumulate in the joints of patients with rheumatoid arthritis, consistent with a role for V-preB+L+ B cells and receptor editing in autoimmune disease.
Meffre
E
E
Laboratory of Molecular Immunology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Davis
E
E
Schiff
C
C
Cunningham-Rundles
C
C
Ivashkiv
L B
LB
Staudt
L M
LM
Young
J W
JW
Nussenzweig
M C
MC
D000361:Agammaglobulinemia / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D016026:Bone Marrow Transplantation / Q000276:immunology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000097:blood; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000276:immunology; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017393:RNA Editing / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D014960:X Chromosome
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007144:Immunoglobulin J-Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D012333:RNA, Messenger; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein