A new discussion in immunology

Thierry Sornasse tsornas at dec5.ulb.ac.be
Thu Jan 27 10:11:06 EST 1994


Hi networkers,

Six month ago the immunological world was peaceful and quiete: just one
costimulatory molecule (B7) and two receptors (CD28 and CTLA4).
Now, we are back to the normal situation: nobody know exactly what could mean and
how could work the different types of B7-like molecules.

First, I want to say that the terminology B7-1 and B7-2 is still unclear since it
seems that in human and and mice there is no equivalence. My personal experience
in mouse costimulatory molecules suggests that B7-2 has most of the functions of
the old B7.

Secondly, most of the work about B7-like molecules has been done on B cells, but
the expression of costimulatory molecules by B cells depends on essentially T
cells. Thus, I think that B cells are quite complicated in the point of view of
the expression of costimulatory molecules.

Thirdly, I work on dendritic cells that seem to play a critical role in the
initiation of the immune response. In fact, DC seem to be the sole APC able to
activate naive Th cells. This potent capacity to activate T cells seems to depends
on the expression of the B7-2 molecules. In fact, DC gain the capacity to
activate naive T cells during a maturation process that involves the upregulation
of the B7-2 molecules. Moreover, immature DC express a low, but significant,
level of B7-? (probably B7-2). 

Fourthly, I think that each type of APC (B cells, DC and Mac) has its owm way to
regulate the expression of the costimulatory molecules.
DC trigger the very first step of the immune response, thus, these cells have to
express the costim. signal indenpendently of T cells activation. The signal
required by DC to express the costim. signal is probably linked to stress stimuli
like wounds or irritation.
Macrophages seem to be very important in response against bacteria and, in fact,
several bacterial molecules have the property to induce the expression of the
costim. signal by Mac.
B cells, as APC, seem to play a major role during the amplification of the
immune response. Moreover, the majority of APC are B cells; in the point of view
of the immune tolerance, B cells should not express the costim. signal in a
resting immune system. Thus, B cells do not express the costimulatory signal
until activated T cells stimulate these cells.

In conclusion, I think that, today, the regulation of the expression of the 
costimulatory molecule by APC is one of the most important field in immunology.
The understanding of the key point would allow us to manipulate the entire immune
response at the earliest step.

( Please forgive me, my english is really bad...)

Best regards

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