What we're trying to do is to understand
what the rules are that govern how
antibodies are made and how they decide
what to target.
I'm Gabriel Victora, I'm an
immunologist.
Immunology is the study of how our
bodies respond to invasion by foreign
substances. Part of the response is
making antibodies, so if you come in with
a virus for example, our bodies are going
to make antibodies to that virus and the
next time you see this virus it's not
going to have any effect on you because
the antibodies are going to stick to it
and then it's gone. Affinity maturation
is the process whereby antibodies become
better and better at binding to their
targets over time. When you first
are exposed to a pathogen you get an
antibody that binds to it but it doesn't
really bind very well. It's enough to get
everything started, but it's not really
a magic bullet. A B cell is the cell that
makes antibodies. Now the B cell gets
recruited into this thing called a
germinal center, and this germinal center
is sort of a boot camp. The B cell tries
to bind to this pathogen, it doesn't bind
very well, then it goes and mutates its
genome and makes little variants. And
out of these, some of them sometimes bind
a little better. The ones that bind
better get selected and they do this
again, and then they mutate again and they
get better again. And as they do this over
and over, there's a sort of Darwinian
framework. The best antibodies survive
and proliferate more, leave more
descendants, so the next time the
pathogen comes in, the immune system has
no trouble clearing it out because it
already trained its antibodies to be
very effective. We use several methods to
study B cells. A lot of our work is
centered on imaging. So we can do things
like intravital imaging where we can
actually look at the response happening
within a live animal, and this gives us
an idea of the cellular dynamics. For
example, while the evolution of B cells
is happening in the germinal center,
they're migrating between different
compartments. They spend some time
mutating in one compartment and some
time being selected in another
compartment. By just looking at how these
cells transit between the compartments,
we can have some idea of how this
evolutionary process works.
Understanding affinity maturation can help in vaccines
in several ways. The issue we have is
making the right antibodies to the spots
that we want in order to neutralize
complicated viruses like influenza
and HIV. Affinity maturation can also be
important for cancer. The germinal
centers, which is where affinity
maturation happens, are essentially
clumps of B cells that are dividing very
very quickly and mutating their genome
and that's a step away from lymphoma.
So understanding how affinity maturation
shapes what is being recognized,
in addition to how well this thing is being
recognized, is where we think the
important science lies. I think I would
be very happy if someone were to read
our rulebook and decide "well this is an
important thing for a vaccine" and use
that and then somehow come up with a
better vaccine for something like
influenza or for HIV. So the impact we
expect to have as basic scientists is
just writing the rule book that someone
can use later to make a vaccine better.
