Infection-fighting B cells go with the flow

Newly formed B cells take the easy way out when it comes to exiting the bone marrow, according to a study published in The Journal of Experimental Medicine.

For infection-fighting T and B cells to defend the body, they must first leave their birthplace—the thymus for T cells and bone marrow for B cells. T cell migration within and eventual exit from the thymus are active processes governed by expression of specific cell surface receptors (called GPCRs) that respond to external attractants and cause the cell to crawl toward exit sites. B cells are retained in the bone marrow by a similar mechanism controlled by a GPCR called CXCR4, which binds to a bone marrow-resident protein and also increases the expression of sticky "integrin" molecules, effectively tethering the cells in place.

But when it comes to leaving the bone marrow, B cells can afford to be lazy. João Pereira and colleagues at Yale University School of Medicine show that B cells actively migrate around the bone marrow with the help of CXCR4 and an integrin called VCAM-1. Without CXCR4, the cells slowed down and many stopped moving entirely, in part due to decreased expression of VCAM-1. For those cells near exit sites, decreased CXCR4 and VCAM-1 allowed them to be passively swept out of the bone marrow with the blood flow.

Why immune cells use different exit strategies in different organs is not completely clear. But the authors suggest that the go-with-the-flow strategy of the bone marrow may be due to its role in the production of red blood cells, which do not express molecules required for active crawling.