Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow.
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.


CONCLUSIONS
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.
Ko
King-Hung
KH
Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China.
Lam
Queenie Lai Kwan
QL
Zhang
Min
M
Wong
Corinne Kung Yen
CK
Lo
Cherry Kam Chun
CK
Kahmeyer-Gabbe
Michelle
M
Tsang
Wai Hung
WH
Tsang
Sze Lan
SL
Chan
Li Chong
LC
Sham
Mai Har
MH
Lu
Liwei
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006720:Homozygote; D015851:Interleukin-7 / Q000494:pharmacology; D038041:Lymphopoiesis / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D018398:Homeodomain Proteins; C503713:Hoxb3 protein, mouse; D015851:Interleukin-7