Consequences of Receptor Editing at the λ Locus: Multireactivity and Light Chain Secretion

• Published in: Proceedings of the National Academy of Sciences - PNAS 2006-07, Vol.103 (30), p.11264-11269
• Main Authors: Doyle, Colleen M., Han, Jiong, Weigert, Martin G., Prak, Eline T. Luning
• Format: Article
• Language: English
• Subjects: Alleles; Animals; Antibodies; Autoantibodies - chemistry; Autoimmunity; Autoimmunity - genetics; B lymphocytes; B-Lymphocytes - metabolism; Biological Sciences; DNA; Gene Rearrangement; Genetic loci; Genotype; Hybridomas; Hybridomas - metabolism; Immunoglobulin Light Chains - chemistry; Immunoglobulin Light Chains - metabolism; Mice; Mice, Transgenic; Models, Molecular; Polymerase chain reaction; Reactivity; Receptors; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Sequence Analysis, DNA
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0604053103

To investigate the manner in which B cells with λ light (L) chains undergo receptor editing, we have studied hybridoma panels from 56R/κ-deleted (kdel) mice. 56R/kdel mice only produce four L chains (λ1, λ2, λ3, and λX). 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 λl 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 λX L chain. Surprisingly, 56R λX B cells are multireactive, binding to a variety of self and nonself antigens, including dsDNA (albeit at reduced affinity compared with the other λ L chains). Another significant population in the 56R/kdel mouse consists of allelically included B cells that express λX along with another L chain. The multireactivity of both 56R λX and 56R λX/λl 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 λ locus that may predispose toward the development of autoimmunity.