ORGANIZATION AND EXPRESSION OF MOUSE λ LIGHT CHAIN IMMUNOGLOBULIN GENES

Abstract

ABSTRACT The four λ light chain constant region (C) genes have been cloned from BALB/c mouse embryo DNA. The Cλ 1 gene segment was previously analyzed (1,2). Each Cλ gene carries its own J segment approximately 1.3 kilobases to its 5′ side which contrasts with both the kappa (K) and heavy (H) chain immunoglobulin gene systems with a cluster of four functional joining (J) sequences 5′ to the constant gene segment(s). The four Cλ genes occur in two clusters: 5′J 3 C 3 J 1 C 1 3′ and 5′J 2 C 2 J 4 C 4 3′. The J DNA segments of λ 2 , λ 3 and λ 4 were sequenced and compared with that of λ 1 . Sequence homology (particularly in the non-coding regions) was greatest between J 1 and J 4 and between J 2 and J 3 which suggests, along with the similar organization of JCJC and crosshybridization of C 1 and C 4 and of C 2 and C 3 , that the two clusters are products of a duplication event. A single variable region (V)λ gene, 5′ of each JCJC cluster, was probably part of this duplication unit. We have confirmed that there are only two Vλ genes in mouse (Vλ 1 and Vλ 2 ), and we have also shown that the Vλ 1 gene segment is joined productively to Cλ 3 in a λ 3 myeloma. Vλ 1 has been found associated only with Cλ 3 or Cλ 1 and in most cases Vλ 2 joins with Cλ 2 (the exceptions allow us to deduce a probable organization of the total λ locus). From these data and from the analysis of germ line and rearranged Vλ genes in myelomas, the two Vλ genes must be interspersed by a JCJC cluster if the looping-out and deletion model is generally used for V-J joining. The organization of the λ locus is most likely: 5′V 2 -J 2 C 2 J 4 C 4 -V 1 -J 3 C 3 J 1 C 1 3′. The λ 4 gene is probably not functional since the J 4 sequence does not contain a valid splice site and has a 2-bp deletion in the signal heptamer sequence 5′ to J 4 . The signal nonamer sequence 5′ to J 3 differs from that of J 1 in two consecutive base pairs and may account for the lower level of λ expression as compared with λ 1 in mouse lymphocytes.