Production of antibodies by modification of an autonomous heavy chain variable domain by gene conversion

Abstract

This disclosure provides, among other things, a transgenic animal that uses gene conversion for antibody diversification, comprising B cells in which the endogenous immunoglobulin heavy chain locus comprises: (a) a functional immunoglobulin heavy chain gene comprising a nucleic acid encoding an autonomous heavy chain (AHC) variable domain; and (b) a plurality of pseudogenes that are operably linked to said functional immunoglobulin heavy chain gene and that donate, by gene conversion, nucleotide sequence to the nucleic acid encoding the AHC variable domain of (a), wherein the pseudogenes are upstream or downstream of the functional immunoglobulin heavy chain gene.

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