Consequences of receptor editing at the λ locus: Multireactivity and light chain secretion

doi:10.1073/pnas.0604053103

Consequences of receptor editing at the λ locus: Multireactivity and light chain secretion

^†Department of Pathology, Committee on Immunology and
*Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637; and
^§Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

Contributed by Martin G. Weigert, June 5, 2006

Abstract

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 λ1 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/λ1 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.

Footnotes

^‡To whom correspondence may be addressed. E-mail: mweigert{at}bsd.uchicago.edu
^¶To whom correspondence may be addressed at:
Department of Pathology and Laboratory Medicine, University of Pennsylania School of Medicine, 405B Stellar Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104.
E-mail: luning{at}mail.med.upenn.edu
Author contributions: C.M.D., M.G.W., and E.T.L.P. designed research; C.M.D. and J.H. performed research; C.M.D., J.H., M.G.W., and E.T.L.P. analyzed data; and C.M.D., M.G.W., and E.T.L.P. wrote the paper.
Conflict of interest statement: No conflicts declared.
Abbreviations:

Abbreviations:

AS,

autoreactive;

HC−,

H chain deficient;

κ deleted,

kdel;

MBP,

myelin basic protein;

VH,

H chain variable region gene segment;

JH,

H chain joining gene segment;

tg,

transgene;

NP,

nonproductive;

PS,

partially self-reactive.
Freely available online through the PNAS open access option.