One-step generation of monoclonal B cell receptor mice capable of isotype switching and somatic hypermutation

Abstract

We developed a method for rapid generation of B cell receptor (BCR) monoclonal mice expressing prerearranged <i>Igh</i> and <i>Igk</i> chains monoallelically from the <i>Igh</i> locus by CRISPR-Cas9 injection into fertilized oocytes. B cells from these mice undergo somatic hypermutation (SHM), class switch recombination (CSR), and affinity-based selection in germinal centers. This method combines the practicality of BCR transgenes with the ability to study Ig SHM, CSR, and affinity maturation.