Consequences of receptor editing at the lambda locus: multireactivity and light chain secretion.
To investigate the manner in which B cells with lambda light (L) chains undergo receptor editing, we have studied hybridoma panels from 56R/kappa-deleted (kdel) mice. 56R/kdel mice only produce four L chains (lambda1, lambda2, lambda3, and lambdaX). They also have a simplified heavy (H) chain repertoire: All B cells start out with a 56R anti-DNA H chain. A few frankly autoreactive 56R lambda1 cells appear to escape into the periphery, but the majority of the peripheral B cell repertoire in 56R/kdel is made up of B cells expressing the 56R H chain with the lambdaX L chain. Surprisingly, 56R lambdaX B cells are multireactive, binding to a variety of self and nonself antigens, including dsDNA (albeit at reduced affinity compared with the other lambda L chains). Another significant population in the 56R/kdel mouse consists of allelically included B cells that express lambdaX along with another L chain. The multireactivity of both 56R lambdaX and 56R lambdaX/lambda1 receptors could contribute to autoimmunity if these B cells were to become activated. Also found among 56R/kdel hybridomas are clones that have inactivated the H chain and secrete only L chains. These clones may represent products of exhaustive rearrangement. Multireactivity, allelic inclusion, and L chain secretion are three consequences of editing at the lambda locus that may predispose toward the development of autoimmunity.
Doyle
Colleen M
CM
Department of Pathology, Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
Han
Jiong
J
Weigert
Martin G
MG
Prak
Eline T Luning
ET
D000483:Alleles; D000818:Animals; D001323:Autoantibodies / Q000737:chemistry; D015551:Autoimmunity / Q000235:genetics*; D001402:B-Lymphocytes / Q000378:metabolism; D015321:Gene Rearrangement; D005838:Genotype; D006825:Hybridomas / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D017422:Sequence Analysis, DNA
D001323:Autoantibodies; D007147:Immunoglobulin Light Chains; D011947:Receptors, Antigen, B-Cell