Impaired B cell development and function in mice with a targeted disruption of the homeobox gene Hex

Hex is a homeobox gene that is expressed in all stages of B cell development except plasma cells. We studied lymphocyte development in the absence of Hex by using the RAG1-deficient blastocyst complementation system because homozygous disruption of Hex is embryonic lethal. Hex(−/−);RAG1(−/−) chimeric mice had severely reduced numbers of mature B cells, pre-B cells, and CD5(+) B cells with a striking 15-fold increase in the percentage of B220(−)CD19(+) cells in the bone marrow. Hex(−/−);RAG1(−/−) chimeric mice failed to generate IgG antibodies to T cell-independent antigens, although their serum IgM levels and antibody responses to T cell-dependent antigens were intact. Therefore, Hex is necessary for B cell development and function and its absence results in a dramatic increase in B220(−)CD19(+) cells.