Targeted deletion of the Hoxa cluster affects B lymphopoiesis through depletion of early lymphoid progenitors

It is well established that Hoxa genes play a critical role in the proliferative capacity of adult hematopoietic stem and progenitor cells, but the importance of Hoxa genes in later stages of hematopoietic differentiation is less clear. Previously, we observed that B-cell numbers were reduced in adult mice in which Hoxa deletion was induced. In the current study, we investigated the requirement of Hoxa genes at different stages of B-cell development. Using an MxCre-inducible conditional knock-out mouse model, we showed that immature B-cell fractions and early lymphoid progenitors were markedly reduced in the absence of Hoxa, whereas mature B-cell populations were found at levels comparable to controls. Deletion of Hoxa genes in B-cell lineage-committed cells, however, did not affect B-cell development despite sustained Hoxa gene expression in immature CD19+ B-cell subsets. Together, these results suggest that the effect of Hoxa on B-cell development originates in early lymphoid progenitor cells.