Restricted immunoglobulin heavy chain mice

A mouse whose germline genome comprises:

• a replacement at an endogenous immunoglobulin heavy chain locus of all or substantially all endogenous VH, DH, and JH gene segments with a single human unrearranged VH1-69 gene segment, one or more human unrearranged DH gene segments, and one or more human unrearranged JH gene segments operably linked to an endogenous immunoglobulin heavy chain constant region nucleic acid sequence comprising at least an endogenous IgM gene at an endogenous heavy chain locus of the mouse,
• wherein the restricted immunoglobulin heavy chain locus is capable of rearranging and forming a plurality of distinct rearrangements, wherein each rearrangement is derived from the single human VH1-69 gene segment, one of the human DH segments, and one of the human JH segments, and wherein each rearrangement encodes a different heavy chain variable domain, and
• wherein the mouse further comprises a population of mature IgMintIgDhi B cells in the spleen, each B cell comprising a distinct rearranged human heavy chain variable region gene sequence derived from the single human unrearranged VH gene segment, the one or more human unrearranged DH, and the one or more human unrearranged JH gene segments.