When eliminating pathogens from the body, antibodies bind to the pathogens to form immune complexes, and activated immune cells then clear the complex. A new study by CiRA researchers in the Journal of Immunology reports a previously unknown role in the clearance by the bone marrow. The function depends on erythropoietin, a hormone that stimulates the bone marrow to produce red blood cells.

The formation of immune complexes is a normal process of the immune system when removing pathogens from the body. However, when the formation of immune complexes exceeds the capacity of the immune system to clear, the complexes are deposited into tissues, where they can eventually lead to inflammation. This phenomenon is observed in the cases of severe infections as well as autoimmune diseases.

According to Dr. Takashi Ito, the lead author of the new study, the liver is thought to be mostly responsible for clearing the excess immune complexes, but other parts of the body such as the bone marrow also deserve investigation.

"We previously found bone marrow endothelial cells express receptors for erythropoietin. Notably, besides the erythropoietin receptor, bone marrow endothelial cells expressed on their surface another receptor, FcγRIIb2, he says.

Erythropoietin is perhaps best known for stimulating the production of red blood cells from the bone marrow, but recent studies have revealed it has immunological effects. FcγRIIb2 is a molecule that binds the Fc portion of antibodies and is crucial for capturing immune complexes.

Notable in the study, an increase in the erythropoietin level in the blood, which is frequently observed in anemic conditions and/or severe bleeding, caused a rise in the FcγRIIb2 expression on bone marrow endothelial cells, leading to the clearance of blood-borne immune complexes. Consistently, FcγRIIb2 deficiency in bone marrow endothelial cells causes the delay of IC clearance from the blood.

CiRA Professor Yoko Hamazaki, who led the project and is an expert of the immune system, explains that endothelial cells in the bone marrow have various unique functions; not only hematopoietic stem cell niche as previously reported, but also the clearance of immune complexes, and current findings suggest that bone marrow has a crucial immunological role under specific circumstances.

"Because erythropoietin is elevated in anemic conditions, our study shows an unknown immunological function for bone marrow endothelial cells when oxygen levels are low. We speculate that this function developed, probably because bleeding sometimes causes infections.

"Our findings also suggest a new avenue to understand the mechanisms of autoimmune diseases caused by poor immune complex clearance and explore the treatment of these patients," she says.

• doi: 10.4049/jimmunol.1901101