Gene conversion contributes to Ig light chain diversity in cattle.

Abstract

In humans and mice, extensive gene rearrangement is the major mechanism of diversification of the primary Ig repertoire. This study shows that cattle depart from this pattern because rearrangement in the light chain locus is sharply limited. Furthermore, in cattle, gene conversion contributes to the diversification of the primary light chain repertoire. Sequencing of germ-line and expressed Vlambda genes revealed three important features. First, the germ line contained a number of Vlambda pseudogenes. In fact, 14 (70%) of the 20 germ-line genes identified and sequenced were pseudogenes, because they had one or more of the following defects: lack of recombination signal sequences at the 3' end, stop codons within the reading frame or truncations, and/or insertions or deletions that resulted in loss of reading frame. Second, Vlambda cDNA from ileal Peyer's patch B cells demonstrated that the light chain repertoire arises from only a small number of V(J) rearrangements. Even though two J genes were identified in the germ line, all of the expressed Vlambda genes examined contained the same J segment, indicating that only a single J gene participates in rearrangement at the lambda locus. Third, a significant number of departures from the germ-line sequences of rearranged Vlambda can be traced to donor sequences of one or more Vlambda pseudogenes. We conclude that a limited number of rearrangements and gene conversion play a role in contributing to the diversification of the primary lambda repertoire. Furthermore, while clear indications of a role for somatic mutation in lambda diversification was seen, V gene rearrangement was not a major factor.