Transcription of immunoglobulin heavy-chain sequences from the excluded allele

Abstract

Production of a functional immunoglobulin heavy-chain gene requires multiple recombination events^1–5. In germ-line cells, segments of the classical variable portion are encoded in separate genetic elements: variable (V), diversity (D) and joining (J) regions^3,5,6. The genes encoding the different clustered constant-region domains (5′-μ, δ, γ³, γ¹, γ^2b, γ^2a, ε, α-3′) are widely separated from the variable region^7–12. During differentiation to immunoglobulin production, one allele containing genes coding for the V, D, J and C segments is rearranged to form a coding sequence for the synthesis of heavy chain. In some cells, the other alleles for heavy-chain segments are rearranged, albeit differently⁸. At the protein level, expression of only one of the alleles is detected (allelic exclusion)^13,14. We report here studies on a class of mouse myeloma MOPC 315 variant cell lines which has lost the ability to produce α heavy-chain protein or mRNA. Hybridization analysis indicates that the functional α allele has been lost. However, these variants synthesize unusual RNA species that include α constant-region sequences. We conclude that this transcription is from the ‘excluded’ allele. Expression of these aberrant RNAs is altered in the presence of a productive gene.