MOP3, a component of the molecular clock, regulates the development of B cells

Abstract

Differentiation and proliferation of haematopoietic progenitor cells occur in intimate contact with the bone marrow microenvironment which is composed of stromal cells and extracellular matrix proteins. MOP3 (also known as brain and muscle Arnt-like protein-1, BMAL1), a master regulator of circadian rhythm, plays important roles in the regulation of cell differentiation and general physical functions. In the present studies, MOP3-deficient mice had significantly reduced levels of B cells in the peripheral blood, spleen and bone marrow compared MOP3(+/-) or MOP3(+/+) littermates. Flow cytometry analysis showed the levels of pre-B cells in bone marrow of MOP3(-/-) mice were similar as that in control mice. Adoptive transfer of MOP3(-/-) bone marrow cells (BMC) to lethally irradiated BALB/c Rag2(-/-) recipients, normal T and B cell development was observed, whereas Adoptive transfer of BALB/c BMC to lethally irradiated MOP3(-/-) recipients, B-cell development was significantly impaired. These results presented herein with MOP3-deficient mice reveal the involvement of MOP3 in the development of B cells, but not other immune cells. The effect of MOP3 on the differentiation of pre-B cells to mature B cells might be mediated by the bone marrow microenvironment. This study also showed a connection between a master regular of circadian rhythm with B-cell development in mice.