Everyone has heard of lymph nodes, the place where our white blood cells (lymphocytes) move into, out of, and around our bodies; and we all know that lymphocytes are important cells for immune health and for fighting disease. But what do the lymphocytes need in order to do the moving around? A breakthrough discovery in how lymphocytes migrate into lymph nodes is reported in a paper appearing in Nature Communications from the laboratory of Richard D. Cummings at Beth Israel Deaconess Medical Center and Harvard Medical School; the first author on the paper is Junwei Zeng, a senior post-doctoral fellow. The group discovered that mutations in mouse B cells specifically engineered in the X-linked gene Cosmc, blocks the synthesis of a carbohydrate termed SC1 on glycoproteins. This loss prevents B cells from homing to lymph nodes of all types, including peripheral lymph nodes and mesenteric lymph nodes. Also, the group showed that loss of a sugar called sialic acid on SC1 led to a loss of homing. Thus, the studies reveal that expression of Cosmc and SC1 are essential for lymphocyte homing.
The engineered animals also exhibit a profound loss of B cells in their circulation in general. Cosmc and SC1 are also required for the normal, progressive development of B cells in the bone marrow. Another intriguing observation is that mechanistically, the B cells lacking Cosmc are defective in responses to key chemokines, including CCL21, as their receptor CCR7 in the mutant mice lacks SC1 and therefore does not properly signal cells, which blocks their ability to move into the lymph nodes. Insights from this work have profound implications for immune function, B cell biology, and chemokine signaling. The findings may also provide insights into sepsis, where sialic acid on lymphocytes may be removed, as well as keys to tumor cell metastasis, as Cosmc is often mutated in certain cancers.
Complete Author list: Junwei Zeng, Mahmoud Eljalby, Rajindra P. Aryal, Sylvain Lehoux, Kathrin Stavenhagen, Matthew R. Kudelka, Yingchun Wang, Jianmei Wang, Tongzhong Ju, Ulrich H. von Andrian, Richard D. Cummings