I was wondering how the body "remembers" viruses after having once overcome them, and while reading this article on the immune system (page 14, Vaccinations), I read:

There are many diseases that, if you catch them once, you will never catch again. Measles is a good example, as is chicken pox. What happens with these diseases is that they make it into your body and start reproducing. The immune system gears up to eliminate them. In your body you already have B cells that can recognize the virus and produce antibodies for it. However, there are only a few of these cells for each antibody. Once a particular disease is recognized by these few specific B cells, the B cells turn into plasma cells, clone themselves and start pumping out antibodies. This process takes time, but the disease runs it course and is eventually eliminated. However, while it is being eliminated, other B cells for the disease clone themselves but do not generate antibodies. This second set of B cells remains in your body for years, so if the disease reappears your body is able to eliminate it immediately before it can do anything to you.

Which made me wonder, instead of vaccinating people with weakened forms of the disease, getting their B cells to activate as described, what would be wrong with growing large colonies of B cells for a given virus and injecting them into someone who has never had the disease so that one can go straight to the last sentence of that paragraph, having many of those B cells in place before the virus is ever experienced?

  • $\begingroup$ the problem is transplantation rejection - the body will reject the injected cells as foreign... $\endgroup$ – MattDMo Jan 8 '14 at 20:29
  • $\begingroup$ There is no other way than vaccination (besides the infection) to bring these B-cells in place. $\endgroup$ – Chris Jan 8 '14 at 21:07
  • $\begingroup$ That's essentially what the vaccines do ! In vivo ! $\endgroup$ – biogirl Jan 9 '14 at 7:36

Remember first that the human body nearly always, although there are exceptions, rejects any non-genetically identical graft placed into it, and therefore one cannot prepare a general colony of B-cells to confer immunity to the population at large. However, in principle, there is no impediment to removing B-cell progenitors in an individual, conditioning them to produce antibodies (which would be an artificial analogue of the natural process of 'Clonal Selection'), and re-injecting these differentiated B-cells into the patient. To my knowledge this process is currently beyond the capacity of our current cell culture techniques, as B-cell differentiation is controlled by an elaborate cell-signaling process, and even if it was feasible, it would remain impractical for several reasons. First, since the B-cell products, antibodies, can be transferred humorally, and should be tolerated by the general population, many existing treatments simply involve injecting antibodies into the patient's bloodstream. Examples of antibodies taken from volunteers' sera are the RhoGam preparations as well as IgG mixtures used to treat certain forms of immunodeficiency. There is a means of growing B-cells in culture to produce antibodies of precise specificity (i.e. monoclonal antibodies - note that clonal selection occurs in a living host for this technique, the B-cells are subsequently harvested then immortalized in culture). Adalimumab is a therapeutic monoclonal antibody.

There is however, very promising work being conducted involving T-cell vaccination, which is technically similar to what you described. The advantage in using T-cells is that these leukocytes can orchestrate an immune response, mobilizing the several, diverse elements of the immune system to respond to a specific antigen. These techniques are being principally researched as cancer treatment regimens.

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    $\begingroup$ And to clarify, the T-cells are coming from the pt, or in more extreme cases HLA matched donors, not just generic T-cells from a cell line or pool. $\endgroup$ – Atl LED Jan 8 '14 at 22:04
  • $\begingroup$ @AtlLED - Presumably. It is essentially adoptive immunity, which by definition would seem to indicate histocompatibility. Being an experimental procedure, there are several methodologies explored to produce these cells. I will try to keep an eye out for a good review article on the preparation methods. A promising aspect of this therapy is that in addition to inducing immunity, the possibility of producing T-regulatory cells may enable us to effectively treat autoimmune diseases and allergies. $\endgroup$ – J. Alfred Prufrock Jan 8 '14 at 22:51
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    $\begingroup$ @J.AlfredPrufrock When we have vaccines available, do you think what the author of the post describes is necessary ? $\endgroup$ – biogirl Jan 9 '14 at 7:36
  • $\begingroup$ @biogirllajja - Direct antibody injection is currently more technically feasible and easier to control. However, there may be niche applications for B-cell adoptive immunity, perhaps if one needed antibody against a very specific epitope. Otherwise I believe T-cell adoptive immunity would initiate a more natural immune response. I have not seen an article that employs the method of B-cell adoptive transfer. I would presume that even if the clone of interest could be isolated, it would be difficult to ensure its proliferation in vivo. $\endgroup$ – J. Alfred Prufrock Jan 9 '14 at 16:14
  • $\begingroup$ Biogirl hit the nail on the head. Vaccines are one of the most beneficial medicines ever invented - in large part this is because they take advantage of a well evolved immune system rather than re-inventing the wheel. $\endgroup$ – johntreml Aug 14 '15 at 12:22

There is also some work with programming a patients own stem cells to become long lived plasma blasts for broadly neutralizing antibodies against HIV (and other diseases I assume). Although you are essentially asking what is harder...eliciting these broadly neutralizing antibodies with traditional vaccine approaches (difficult), or working out the complex cell signalling pathways to get from stem cell to long lived plasma blast. Even the pathway from memory b-cell to plasma blast is still not entirely understood, so we are several years away from this approach.

It is so appealing though for so many reasons. Once you have a plasma cell secreting a broadly neutralizing antibody, you have it forever (or at least many many years). This circumvents the extremely expensive antibody therapeutic approach as large quantities of these proteins are indeed just expensive to make as with all protein therapeutics.


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