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

To investigate the manner in which B cells with light (L) chains undergo receptor editing, we have studied hybridoma panels from 56R -deleted (kdel) mice. 56R kdel mice only produce four L chains ( 1, 2, 3, and X). 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 1 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 X L chain. Surprisingly, 56R X B cells are multireactive, binding to a variety of self and nonself antigens, including dsDNA (albeit at reduced affinity compared with the other L chains). Another significant population in the 56R kdel mouse consists of allelically included B cells that express X along with another L chain. The multireactivity of both 56R X and 56R X 1 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 locus that may predispose toward the development of autoimmunity.