Molecular insight into B cell biology
The adaptive immune system comprises our specialised weapon against viruses and bacteria. One of the central players, the B lymphocyte is responsible for producing effector proteins called antibodies. These antibodies bind to and neutralise the antigens on invading pathogens. Upon re-exposure to the same infectious agent, high affinity antibodies are rapidly produced, rendering B cells the orchestrators of immunological memory. This process of selection occurs in germinal centres (GCs) within secondary lymphoid organs such as the spleen and lymph nodes. The scope of the EU-funded 3W-RGB (Identification of whether, in which aspects and by which function, a RNA binding protein, KH-type splicing regulatory protein governs development and function of B cell, a type of white blood cell) project was to understand B cell biology and facilitate vaccine development to prevent B cell-related diseases. The study focused on the role of microRNAs, the short RNAs that regulate gene expression by promoting mRNA decay. In particular, researchers were interested in miR-155, given its role in antibody production and in KH-type splicing regulatory protein (KSRP) that is responsible for its biogenesis. The consortium worked under the hypothesis that KSRP is an important gene regulator of B cell biology and set out to delineate the mechanism of its activity. Using transgenic mice deficient in KSRP researchers concluded that this RNA-binding protein did not play a major role in GC B cells. Next, using a miR-155 reporter mouse strain they discovered that miR-155 was co-expressed with the proto-oncogene c-Myc. Further insight into this co-operation indicated that miR-155 protected c-Myc+ B cells from apoptosis and allowed their clonal expansion. Taken together, the findings of the 3W-RGB project support a central role for miR-155 in affinity maturation of B cells in GCs. Importantly, they explain a synergistic oncogenic role of the miR-155-c-Myc axis in B cell-associated cancers.
Keywords
B cell, vaccination, antibodies, germinal centres, Mir-155, KSRP, c-Myc
