re immunol. of B7-1 and B7-2

Thierry Sornasse tsornas at dec5.ulb.ac.be
Wed Feb 2 06:27:31 EST 1994


Dear Networkers,

In article <2ijdljINN5dn at dns1.NMSU.Edu>, smori at nmsu.edu (Shahram Mori) writes:
|> 
|> dear immunetters
|> I have seen very interesting posts on B7-1 and B7-2 by Lee Wetzler and thierry
|> sornasse. However I am still a little confused on a couple of experiments that
|> they did to get at B7-2. My first point of confusion is that if B7-2 is the
|> major costimulatory protein then what is the function of B7-1 ( since its
|> m RNA is not even produced till about 24-48hrs after the first signal is
|> received by the T cell in which case would be to differentiate)?
|> There could be a couple of possibilities.
|> 1) B7-1 is stimulated under different conditions than B7-2 and that's the
|> reason for the group seeing low b7-1 under those conditions.
|> 2) B7-1 has other purposes activation is not its major role.
|> 
|> My second point of confusion was that just knowing that B7-1 is not
|> produced  early enough one can't assume that
|> 1) B7-1 is not the major co-stimulatory signal, because different antigens
|> might preferentially induce one or the other of B7's.
|> 2) Just because B7-2 is produced early that it's the major factor. Because we
|> all know that there are translational regulations and post translational
|> modifications that might be going on and this might affect the expression
|> of B7-2.
|> If B7-1 and B7-2 do have the same function then why is it necessary to have
|> both?
|> 
|> Thanks again for everybody that responded to my " new discussion in
|> immunology" post.
|> Cheers
|> ShahramI guess posting is better so  everyone who is interested can read it.
 
This article reflect the puzzling problem of the function and the regulation of
the different types of B7.

About the fact that B7.2 would be the major costimulatory signal, I think that
for dendritic cells it is a reality. In fact, purified-mature DC are the best T
cell activator among the APC population. This capacity to activate T cells is
correlated with the level of expression of the B7.2 molecule. Mature DC express
very high level of B7.2 but very level of B7.1.

We can consider the problem by the point of view of T cells. I think that the
activation of a NAIVE T cell depends totally on the expression of the costim.
signal by the APC while memory T cell or an activated T cell would require a
lower costim signal to be activated. Thus, the immune system requires at the very
first step of its activation a strong costim. signal but later, when activated T
cells appear, this costim. signal could decrease. Moreover, I think that the
possibility to split the role of the costim. signal in two functions (early
and late) could lead to a better regulation of the immune response. In fact, we
could imagine that the B7.1 would be expressed only by APC if the level of
activation of T cells is sufficient. I think that this regulation would occur
essentially with B cells. Activated T cells express the CD40 counter-receptor
(gp39) and B cells express the CD40. It seems that the cross-linking of the CD40
by activated T cells is one of the signals required by B cells to express the
costim. signal. I do not know if there is any publication about the expression of
the different sub-types of B7 in this conditions. 
Once APC express the "late" type of the costim. signal, the immune system could
start a second phase of the immune response.
If I remember well, I think that some autors have came up with the idea that the
B7.1 could play a negative role during the immune response. Following this
idea, in the late phase of the immune response the neo-expression of the B7.1
molecule could lead to down regulation of the entire immune response. The 
difference between no costimulatory signal and the B7.1 would rely on the fact 
that in the first case T cells would be anergized and in the second case T cells 
would simply deactivated. 

The regulation of the synthesis, and thus the expression, of the different types 
of B7 is still a problem without answers. 
In our laboratory, we are not sure that B7.1 and B7.2 are coded by different
genes but in fact we think that B7 subtypes could be isoforms of the same molecule
as it occurs with the CD45 molecule. It is just an hypothesis to explain some
strange results we got last week but it could lead to a different perception of
the problem.

Sorry, I have to stop here, my dendritic cells are waiting for me.

Best regards

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