Speed-dating between antigen presenting cells and lymphocytes
The latest discovery by the Spatial-temporal regulation of antigen presentation team (Inserm - U932/Institut Curie) led by Ana-Maria Lennon-Duménil concerns the meeting between B-lymphocytes and antigen presenting cells. "This is a key moment in adaptive immune response", she recalls. B-lymphocytes learn to recognise the enemy that they then have to eliminate through their ability to produce antibodies. If the meeting goes wrong, the "aggressivity" of the B-lymphocytes may be directed towards the wrong enemy or be insufficiently effective. It is therefore essential so that the immune system can eliminate bacteria, parasites, fungi, viruses or even tumour cells."
Before the meeting...
After the meeting, the antigen presenting cell has transmitted to the B-lymphocytes >a characteristic fragment, an antigen, from the potentially threatening microorganism or cell which has to be eliminated. After the approach phase, the B-lymphocyte sticks to the antigen presenting cell to form an immunological synapse. This is where the exchanges required for activation and learning by the B-lymphocytes take place.
The formation of this place of exchange depends on the plasticity of the B-lymphocytes, especially their ability to adapt to the polarity of the meeting. To do so, the cytoskeleton, made of microtubules that are mainly used for intracellular transport and an actin network that controls their shape and movement, must reorganise to meet the new constraints and ensure transport of the ingredients required for the B-lymphocytes' response.
... and afterwards for the centrosome
"The centrosome is the place where the microtubules get organised, guiding the change in polarity within the lymphocytes", explains Ana-Maria Lennon-Duménil, Inserm director of research. We have shown that, before the meeting when the lymphocytes are resting, the centrosome is closely linked to the cell nucleus. When it comes into contact with the antigen presenting cell, the lymphocyte is activated. The centrosome detaches from the nucleus and relocates near the immunological synapse."
The Arp2/3 protein complex seems to be one of the molecular instigators of this change in position. It initiates the polymerisation of the filaments forming the actin network. The team's work shows that prior to activation of the B-lymphocyte, part of the Arp2/3 complex is linked to the centrosome allowing local polymerisation of actin which maintains the physical link between the centrosome and the nucleus. When the lymphocyte is activated, the Arp2/3 complex disappears from the surroundings of the centrosome, thus reducing its ability to assemble actin filaments. The centrosome can cut the cord with the cell nucleus and position itself near the immunological synapse. "The polarity of the lymphocytes is thus modified and the network of microtubules reassembles to meet the new needs following activation of the lymphocyte", the scientists explains. With this discovery, Ana-Maria Lennon-Duménil has pushed back the boundaries of knowledge about the activation of B-lymphocytes and has opened up new avenues for the development of more effective immunotherapy.