Members at IFReC, Osaka University provide new insights on why the tumor suppression gene Foxo1 can actually be the cause of some cancers.

To understand how B cells cycle in the germinal center, Prof. Tomohiro Kurosaki, who led the project, set his eyes on Foxo1. "Foxo1 is a tumor suppressor gene, but it promotes B cell proliferation in the germinal center," he said.
Normally, the suppression of Foxo1 expression enables cells to proliferate. Even B cells outside the germinal center will proliferate when Foxo1 is suppressed. However, some lymphomas are associated with activated Foxo1, and Kurosaki and his team observed that inside germinal centers, B cells with Foxo1 suppressed will actually lower in numbers.
Transferring the mutant B cells into mice, the researchers further showed that Foxo1 has a vital role in the cycling of B cells between light and dark zones.
"We found B cells remained in the light zone," said Kurosaki of the Foxo1-deficient B cells.
The dark zone is where B cells undergo proliferation. When in the light zone, B cells are selected by follicular helper T (TFH) cells for migration to the dark zone. Kurosaki found that without Foxo1, B cells are not selected at all.
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BCR, or B cell receptors, describe the unit on the B cell that binds to the invasion and from which B cells are selected to proceed with the cycling. Moreover, even if the Foxo1-deficient B cells could be manipulated to be selected by the TFH cells, they still did not proliferate, suggesting another factor besides Foxo1 is also imperative to cycling.
The findings provide important new knowledge on antibody production by the body and also the development of certain cancers.
"Even though Foxo1 is a tumor suppressor gene, paradoxically its activity is associated with lymphomas," said Kurosaki. This study provides new candidate molecular targets for the treatment of such lymphomas.
Source-Eurekalert