GENE CONVERSION CONTRIBUTES TO IG LIGHT-CHAIN DIVERSITY IN CATTLE

In humans and mice, extensive gene rearrangement is the major mechanis m of diversification of the primary Ig repertoire, This study shows th at cattle depart from this pattern because rearrangement in the light chain locus is sharply limited, Furthermore, in cattle, gene conversio n contributes to the diversification of the primary light chain repert oire, Sequencing of germ-line and expressed V lambda genes revealed th ree important features, First, the germ line contained a number of VA pseudogenes, In fact, 14 (70%) of the 20 germ-line genes identified an d sequenced were pseudogenes, because they had one or more of the foll owing defects: lack of recombination signal sequences at the 3' end, s top codons within the reading frame or truncations, and/or insertions or deletions that resulted in loss of reading frame, Second, V lambda cDNA from ileal Peyer's patch B cells demonstrated that the light chai n repertoire arises from only a small number of V(J) rearrangements, E ven though two) genes were identified in the germ line, all of the exp ressed V lambda genes examined contained the same J segment, indicatin g that only a single J gene participates in rearrangement at the lambd a locus, Third, a significant number of departures from the germ-line sequences of rearranged V lambda can be traced to donor sequences of o ne or more V lambda pseudogenes, We conclude that a limited number of rearrangements and gene conversion play a role in contributing to the diversification of the primary lambda A repertoire, Furthermore, while clear indications of a role for somatic mutation in lambda diversific ation was seen, V gene rearrangement was not a major factor.