ImmunoglobulinλGene Rearrangement Can PrecedeκGene Rearrangement

Abstract

Immunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci:κandλ.It has been reported thatκloci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearrangedλ-chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at theκlocus, and that only upon failure to produce a functionalκchain is there an attempt to rearrange theλlocus; and (b) the stochastic theory, which postulates that rearrangement at theλlocus proceeds at a rate that is intrinsically much slower than that at theκlocus. We show here thatλ-chain genes are generated whether or not theκlocus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.