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 or known subtype (λ1, λ2, or λ3). For 11 out of 12 λ chains, the rearrangement was Vλ1 → Jλ1; for 9 out of 9 λ2 chains, it was Vλ2 → Jλ2; and for 8 out of 9 λ3 chains, it was Vλ1 → Jλ3. 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 Vλ1-Jλ1 for 28 λ1 chains, Vλ2-Jλ2 for 10 λ2 chains, and Vλ1-Jλ3 for 5 λ3 chains. Of the combined total of 74 chains there were 3 with unusual Vλ rearrangements, all involving the Vλ2 gene segment: for 2 of these unusual chains, the encoding segments were Vλ2-Jλ1-Cλ1 and for one they were Vλ2-Jλ3-Cλ3. Thus, the results for all 74 λ chains show that, in contrast to the apparent unrestricted Vκ→ Jκ rearrangements for κ chains, for each of the 3 murine λ-chain subtypes V-J recombination is severely restricted: the Vλ gene segment expressed in λ1 and λ3 chains was nearly always Vλ1 (95% and 93%, respectively), whereas in λ2 chains it was without exception Vλ2 (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' Vλ2-Jλ2Cλ2Jλ4Cλ4-Vλ1-Jλ3Cλ3Jλ1Cλ1 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 JλCλ segments, and (ii) Vλ rearrangement to the upstream (5') cluster is very rare and possibly may not take place at all.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Issue number||8 I|
|State||Published - Jan 1 1984|
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