Australian researches have identified a protein molecule that could be the key to efficacy of vaccination. Cell surface receptor, EBI2, is the determining factor, say scientists with the Garvan Institute of Medical Research, Sydney.
As soon as we are infected with a virus or other microbe, we start generating antibodies. But only some B cells make high quality antibodies over a period of several weeks, while others will tend to churn out low quality antibodies, sacrificing quality for speed.
Drs Dominique Gatto and Robert Brink from the Garvan Institute have demonstrated in mice that inhibiting EBI2 leads to generation of B cells that produce high quality antibodies, thus becoming an insurance against future infection.
Early in life all B cells are the same. They lie dormant in our bodies, with an antibody on the cell surface. If the antibody sticks onto an invading molecule, the B cell gets activated and starts to divide, resulting in thousands of clones.
Roughly half of those clones become short-lived 'plasma cells', which change from having copies of the antibody on their surface to making large amounts of secreted antibodies, which disperse through the body, labelling invaders for destruction. While these 'low affinity' antibodies are far from perfect, they can hold many infections at bay.
The other B cell clones migrate to areas known as 'germinal centres', specialised microenvironments where B cells start incorporating random mutations into their antibody genes, trying to create a new antibody that will more exactly match the invader. This process takes time, with thousands of rejects created before a few rare cells are selected to survive. These cells eventually produce the high affinity antibodies that can attack and eliminate invading microbes with great potency. They also turn into 'memory B cells', that have long lives and provide immunity against a similar infection in the future.
''As B cell biologists, it is very important for us to understand why these cells behave as they do,'' said project leader Brink. ''There was evidence to suggest that when B cells went to germinal centres to make high affinity antibodies, they lost their EBI2 receptor.''
''We tested the hypothesis that the receptor was driving the cells one way or another by creating mice without the EBI2 receptor. In those mice, 85 per cent of the B cells went straight to germinal centres, while only 15 per cent turned into plasma cells. In normal mice, it's an even split.''
''We further proved the hypothesis with the inverse of the knockout experiment. By injecting normal B cells with an extra copy of the EBI2 gene, the extra gene remained even after B cells had shut down their own copy of EBI2. This made it impossible for B cells to go to the germinal centre, and the mice had a huge plasma cell response.''
''We can now see that having this molecule switched on is important for short-term protection. Having it switched off is important for our long-term response.''
Their findings are published online in the prestigious international journal Immunity
, ahead of the 21 August print issue.