Australian scientists have extracted information that could help us fight certain cancers and autoimmune diseases. Their study of blood samples from patients recovering from bone marrow transplants reveals mechanisms by which certain immune system cells, B cells, behave.
B cells, the immune cells that produce antibodies, start their development in the bone marrow and complete it in peripheral blood and tissues. The developmental process in humans can be easily studied in people who have had their bone marrow destroyed and then reconstituted from donors, because clinical samples are collected at defined periods of time following the transplant.
A team at the Garvan Institute of Medical Research in Sydney, identified an important checkpoint in the development process where the body gets rid of rogue B cells. These 'rogue' B cells are the cause of some autoimmune diseases, such as lupus, because they see their own 'self' body as the enemy and proceed to attack it as though it were a foreign germ.
Their findings, which describe a ‘molecular signature’, or fingerprint, for B cells at this crucial stage of development were published in the international journal Blood.
"By identifying exactly where B cells are in their stage of development, you can better understand and target specific B cell diseases” said one researcher Dr Stuart Tangye.
The researchers identified two subsets of human transitional B cells based on the differential expression of the CD21 surface molecule. At a particular stage of their development, a subset of B cells expressed low levels of CD21, elevated levels of Lymphoid enhancing binding factor-1 (LEF-1), a transcription factor highly expressed by immature lymphocytes, and they also produced higher amounts of autoreactive (anti-self) antibodies.
“Acute Lymphoblastic Leukaemia, for instance, may be a malignancy of the B cell subset we’ve described. As we now know what the normal counterpart of the diseased B cell looks like, we are in a position to learn more about that type of leukaemia,” said Dr Tangye.
“In the case of lupus, an autoimmune disease where antibodies are produced that recognise self DNA, there seems to be a problem getting rid of the self-reactive B cells - at this point of the development process.”
The researchers believe this knowledge of which genes are expressed in B cell subsets at different stages of maturity, may help identify more specific therapeutic targets that will improve the treatment of diseases resulting from self-reactive or malignant B cells.