B cells- root of many illnesses why? (Lupus example)

[amanda more]

Hi, I have a biomedical engineering background and would love to get into the nitty gritty of the detailed biochemistry here. I can again look up pubmed articles to support this. I like to try to drill down to the underlying cause then work from there. Many medical treatments never touch the underlying cause so I am not discounting the many methods using ways removed from this. But it provides a deep understanding if we are to a point to "get it" first at this level.

two b-cells O O

 

they see a substance <<<<<<<<<<

 

 

They both get activated

 

 

then one quiets

O

but the other stays active

 

The first one is a normal bcell that has seen a substance which is actually part of the person's own body. The second one is the essence of Lupus and also reacts. This appears to be independent of all the other cell signaling factors acting on or with the bcell. Why? And even if one has the bad luck to have selfreacting bcells can they be messed with to then have them do selfdeath or switch back?

[amanda more]

Aberrant B cell receptor-mediated feedback - A feature of human autoimmune disease is that it is largely restricted to a small group of antigens, several of which have known signaling roles in the immune response (DNA, C1q, IgGFc, Ro, Con. A receptor, Peanut agglutinin receptor(PNAR)). This fact gave rise to the idea that spontaneous autoimmunity may result when the binding of antibody to certain antigens leads to aberrant signals being fed back to parent B cells through membrane bound ligands. These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 and 7 (which can bind DNA and nucleoproteins) and PNAR. More indirect aberrant activation of B cells can also be envisaged with autoantibodies to acetyl choline receptor (on thymic myoid cells) and hormone and hormone binding proteins. Together with the concept of T-cell-B-cell discordance this idea forms the basis of the hypothesis of self-perpetuating autoreactive B cells.^[14] Autoreactive B cells in spontaneous autoimmunity are seen as surviving because of subversion both of the T cell help pathway and of the feedback signal through B cell receptor, thereby overcoming the negative signals responsible for B cell self-tolerance without necessarily requiring loss of T cell self-tolerance.

This is from wikipedia autoimmunity http://en.wikipedia.org/wiki/Autoimmunity

 

One thing I may have misunderstood. In this example we probably all have the Lupus bcell somewhere in our bodies- some bcells who remain activated and don't quiet. Those who have Lupus though have more of them. Anyone have a handle on this?