Light chain editors of anti-DNA receptors in human B cells.
Receptor editing is a mechanism of self-tolerance used in newly generated B cells. The expressed heavy (H) or light (L) chain of an autoreactive receptor is replaced by upstream V genes which eliminate or modify autoreactivity. Editing of anti-DNA receptors has been characterized in anti-DNA transgenic mouse models including 3H9, 3H9/56R, and their revertant 3H9GL. Certain L chains, termed editors, rescue anti-DNA B cells by neutralizing or modifying DNA binding of the H chain. This editing mechanism acts on the natural H chain repertoire; endogenous H chains with anti-DNA features are expressed primarily in combination with editor L chains. We ask whether a similar set of L chains exists in the human repertoire, and if so, do they edit H chains with anti-DNA signatures? We compared the protein sequences of mouse editors to all human L chains and found several human L chains similar to mouse editors. These L chains diminish or veto anti-DNA binding when expressed with anti-DNA H chains. The human H chains expressed with these L chains also have relatively high arginine (Arg) content in the H chain complementarity determining region (H3), suggesting that receptor editing plays a role in establishing tolerance to DNA in humans.
Gwen Knapp Center for Lupus and Immunology Research, Department of Pathology, University of Chicago, Chicago, IL 60637.
Olga
O
Kalinina
Yue
Y
Wang
Kevin
K
Sia
Marko
M
Radic
Pierre-André
PA
Cazenave
Martin
M
Weigert
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000378:metabolism*; D000915:Antibody Affinity; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D022801:Complementarity Determining Regions / Q000235:genetics; D017124:Conserved Sequence; D004247:DNA / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D017634:Self Tolerance; D017386:Sequence Homology, Amino Acid; D055815:Young Adult
D000974:Antibodies, Antinuclear; D022801:Complementarity Determining Regions; C033365:DNA receptor; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D011956:Receptors, Cell Surface; D004247:DNA