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.
Bogue
Clifford W
CW
Yale Child Health Research Center, Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06519, USA. clifford.bogue@yale.edu
Zhang
Ping-Xia
PX
McGrath
James
J
Jacobs
Harris C
HC
Fuleihan
Ramsay L
RL
D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000502:physiology*; D005801:Genes, Homeobox / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000032:analysis; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D014157:Transcription Factors
D018941:Antigens, CD19; C513080:Hhex protein, mouse; D018398:Homeodomain Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014157:Transcription Factors; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens