Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow

• Published in: Experimental hematology 2007-03, Vol.35 (3), p.465-475
• Main Authors: Ko, King-Hung, Kwan Lam, Queenie Lai, Zhang, Min, Yen Wong, Corinne Kung, Chun Lo, Cherry Kam, Kahmeyer-Gabbe, Michelle, Tsang, Wai Hung, Tsang, Sze Lan, Chan, Li Chong, Sham, Mai Har, Lu, Liwei
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Apoptosis - drug effects; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Bone Marrow Cells - immunology; Bone Marrow Cells - metabolism; Cell Proliferation - drug effects; Disease Models, Animal; Hematology, Oncology and Palliative Medicine; Homeodomain Proteins - genetics; Homeodomain Proteins - physiology; Homozygote; Interleukin-7 - pharmacology; Lymphopoiesis - immunology; Mice; Mice, Knockout; T-Lymphocytes - immunology; T-Lymphocytes - metabolism
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/j.exphem.2006.10.014

Objective Hox genes are involved in hematopoietic lineage commitment and differentiation. In this study, we investigated the roles of Hoxb3 in hematopoiesis by examining the phenotypes of a Hoxb3 knockout mutant mouse line. Results Despite previous reports describing the apparently normal phenotype of these mutant mice, we found that by 6 months of age, Hoxb3−/− mice began to exhibit significantly impaired B lymphopoiesis in the bone marrow (BM). The cellularity was reduced by 30% in mutant BM compared to age- and sex-matched heterozygous and wild-type controls. The population size of B220+ CD43+ progenitor B cells showed a twofold reduction while that of B220+ CD43− IgM− precursor B cells was decreased fivefold. Sorting-purified Hoxb3−/− progenitor B cells displayed significantly reduced proliferative response to IL-7 in culture, consistent with our findings of reduced IL-7 receptor expression in Hoxb3−/− progenitor B cells. However, the peripheral B cell pool in the spleen of Hoxb3−/− mice was maintained with a similar size as in wild-type littermates. Conclusion Analysis of T-cell development in the thymus and B1 cell compartment in the peritoneal cavity showed no significant changes. Thus, our findings suggest that the Hoxb3 gene plays an essential role in regulating B lymphopoiesis in the BM of adult mice.