Restricted Association of V and J--C Gene Segments for Mouse λ Light Chains

The frequencies of diverse rearrangements of variable (V)λ to joining (J)λ gene segments were examined by Southern blot hybridization in 30 murine B-cell lines, each producing an immunoglobulin λ light chain of known subtype (λ 1, λ 2, or λ 3). For 11 out of 12 λ 1 chains, the rearrangement was Vλ 1-> Jλ 1; for 9 out of 9 λ 2 chains, it was Vλ 2-> Jλ 2; and for 8 out of 9 λ 3 chains, it was Vλ 1-> Jλ 3. Similar results were obtained by considering the partial or complete sequences at the amino acid or cDNA level of 44 other λ chains (24 previously described): for 43 of these chains the rearranged V-J gene segments were evidently Vλ 1-Jλ 1 for 28 λ 1 chains, Vλ 2-Jλ 2 for 10 λ 2 chains, and Vλ 1-Jλ 3 for 5 λ 3 chains. Of the combined total of 74 chains there were 3 with unusual Vλ rearrangements, all involving the Vλ 2 gene segment: for 2 of these unusual chains, the encoding segments were Vλ 2-Jλ 1-Cλ 1 and for one they were Vλ 2-Jλ 3-Cλ 3. Thus, the results for all 74 λ chains show that, in contrast to the apparently unrestricted V kappa -> Jkappa rearrangements for kappa chains, for each of the 3 murine λ -chain subtypes V-J recombination is severely restricted: the Vλ gene segment expressed in λ 1 and λ 3 chains was nearly always Vλ 1 (95% and 93%, respectively), whereas in λ 2 chains it was without exception Vλ 2 (19 out of 19 chains). Therefore Vλ -Jλ combinatorial variation is not a significant source of amino acid sequence diversity of λ chains of inbred mice. If the order of the λ gene segments is 5' Vλ 2-Jλ 2Cλ 2Jλ 4Cλ 4-Vλ 1-Jλ 3Cλ 3Jλ 1Cλ 1 3', as suggested previously and by the present findings, it appears that (i) when a Vλ gene segment rearranges in a developing B cell it ordinarily recombines with a Jλ gene segment in the nearest downstream (3') cluster of Jλ Cλ segments, and (ii) Vλ rearrangement to the upstream (5') cluster is very rare and possibly may not take place at all.