Restricted association of V and J-C gene segments for mouse lambda chains.

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