Please, describe your search mechanism, and also please list a few papers that describe research at least related to your interest.  It is not clear from your post just what it is you hope to glean from offered answers.

Williamj R Buckley, here is part of an essay Iwrore some years ago. Hope it answers your question exactly. 

What is involved  in making a specific antibody to a specific antigen? The immune system recognizes an unfamiliar epitope on a molecule and a dance of enzymatic activity begins where V and J gene segments are cleaved and spliced, d-nucleotidyl transferases may insert nucleotides in V and D segments, with as many possible choreography as there are possible antibody specificity. The master choreographer for all these possible scenarios must by necessity reside ultimately in our germ cell line. Ultimately, even if some predisposed somatic mutations take place, we must assume that this ability to respond to any antigen, even the myriad of synthetic antigens created in modern laboratories, is inherited. And therein lies the problem.

Back in 1976, I wrote the following to Dr. Marvin Fishman, one of the pioneers in Immune RNA research at St Jude Children Research Hospital:

“It is hard to conceive how genes for antigens that had yet to come into existence would have been preserved through eons of evolution since there would be absolutely no natural selective pressure to insure their continuation in the germ line. One possible mechanism for the generation of antibody diversity is the formation of informational RNA in certain specialized cells in response to a given antigen and the distribution of this RNA to other cells involved in the immune response.

Your work has shown the existence of I-RNA and its informational role. Its mechanism of formation is not yet known. It seems unlikely to me, for reasons stated above, that the macrophages responsible for making I-RNA carry this information in their genome. It would have been evolutionarily simpler to develop an enzyme system capable of making the appropriate I-RNA when it comes in contact with the Ag in question. This system would only have to provide information for the combining site of an immunoglobulin. Once this piece of RNA is made, it can be incorporated into the macrophage’s genome by the reverse transcriptase at the appropriate site and then the information for a whole specific immunoglobulin could be released through transcription. This hypothesis can be checked by adding an inhibitor of the reverse transcriptase along with the antigen. This should prevent release of I-RNA capable of coding for a whole Ab in a cell free system. Actinomycin-D would also inhibit the release by the macrophages of I-RNA...”

What I was proposing to Dr. Fishman and all of my professors at the time was the existence of “Reverse Translatase”, an enzyme that could read the epitope site of a foreign protein and encode the proper nucleic acid sequence that would then become the template on which the amino acid chain that would constitute an anti-epitope could be assembled. At this point, let me provide a little background on Immune RNA.

It was found that a percentage of macrophages from peritoneal exudates, induced by injection of mineral oil into the peritoneal cavity of mice, incubated in vitro with antigens the donor animals never came in contact with, could process these antigens and elaborate specialized RNA that could transfer immunity. The first hints that macrophages played a crucial role in antibody production came in the late 50s when Fishman et al. showed that antibody production to a specific antigen could be initiated in vitro in lymph node fragments after their stimulation with cell free extract from macrophages that had been incubated with the antigen in question. It was shown that adding the antigen itself to these fragments initiated no response. Only the extract from the macrophage-antigen soup elicited a response. Furthermore, treating this extract with RNase before adding it to the lymph node fragments totally destroyed its capacity to stimulate antibody production in those fragments. Immune RNA was born. Later the standard experiments were conducted with spleen cell cultures mainly instead of lymph node fragments.

It seems to me that the most economical system that could have evolved is the capability to process antigens with a Reverse Translatase system of enzymes that would then transmit information that would be incorporated in the hypervariable or combining site of a specific antibody. This new RNA could then be inserted in the appropriate gene segment of B cells via Reverse Transcriptase that would henceforth become memory cells capable of a secondary immune response. It would be a much more efficient and more easily attainable way for nature to achieve specificity rather than the cleavage, splicing and recombination of gene segments in a predetermined choreography with a billion variations. A few experimental facts that were known in the 70s on the elaboration of I-RNA seem, if not confirm, to at least suggest such a hypothesis.

1-The addition of Actinomycin D, rifampicin or dimethylrifampicin inhibit the formation of I-RNA by these specialized macrophages indicating the need for RNA polymerase and Reverse Transcriptase activity for its formation. This is what one would expect if a new nucleic acid chain was formed by reverse translation and then had to be incorporated into the macrophage’s genome before a completed I-RNA could be transcribed.

2-And this is a most important point: the formation of RNA-antigen complexes that is found in those peritoneal exudates macrophages as a precursor to the completed I-RNA strands was not inhibited by either Actinomycin D or rifampin suggesting that the RNA formed in those complexes during the antigen processing phase was not transcribed but formed in another manner, perhaps by Reverse Translatase.

3-The ability of I-RNA to stimulate antibody production in spleen cell cultures is not inhibited by Actinomycin D nor rifampicin indicating clearly that there is no need for transcription of any gene for the antibody produced. The information for the whole antibody must be completely contained in the I-RNA..

So the evidence suggests that some antigens are first sequestered by a specialized sub-population of macrophages that process them by first forming RNA-antigen complexes. That RNA does not need to be transcribed from any gene region since its formation is not blocked by inhibitors of RNA polymerase, but is perhaps elaborated by a Reverse Translatase that probably makes up the major protein component of those complexes. The next step seems to be incorporation of that RNA into a gene region by reverse transcriptase and then transcription of the complete strand of I-RNA. This I-RNA is released and picked up by B lymphocytes that can then initiate an antibody response. Once this I-RNA is incorporated in the appropriate gene region of the B cells by reverse transcription, they become committed memory cells capable of a more rapid secondary immune response if stimulated again by the antigen.

Proof of the existence of such an enzyme would be in RNA-DNA hybridization studies. If one could extract the RNA from the RNA-protein complexes that seem crucial as a precursor to the formation of I-RNA in those specialized cells and show that it would only hybridize with DNA from V or D gene segments of committed memory B cells but not unsensitized B cells from the same donor, it would be a powerful argument for the existence of reverse translation. An assay for such an enzyme or enzyme system by demonstrating uptake of an appropriate tritiated nucleic acid could also be attempted. Its most likely source, if it exists, would be those RNA-protein complexes found in peritoneal exudates cells exposed to antigen.

Prof Laham,

 I am a haematologist and in the line of thinking of prions I suggested a hypothesis of reverse translatases and tried to publish my hypothesis way back in 1987 in various international and national journals . I was not aware of your line of thinking at that point of time. However as nobody will accept my hypothesis and my lab was not equipped to test the hypothesis either I kept on thinking how to go ahead with the project later on I wrote a letter to Prof stanley Prusiner for his Idea and help . Unfortunately probably due to his punishing schedule and   considering some unkonwn fellow  is writing , may be rubbish he did not give me any answer . I felt I must some where write about my idea and as you can see from the abstract below it was published in Indian journal of haematology with a minor spelling mistake in the title. Now seeing your response I feel good that I was not the only one thinking about it . Our line of thinking was different but was leading to the same conclusion . i strated with how pathogenic prions reproduce , an area which is still full of hypothesis and your idea on macrophage / lynphoid cells is very close . at that time I felt Tdt like enzyme which works without a template could be such an enzyme though.

Ghosh K

National Institute of Immunohaematology, Mumbai

Do reverse translatses exist?

Indian Journal of Hematology and Blood Transfusion. 1999 Mar; 17(1): 3-4

ABSTRACT: Central dogma emphasized that "DNA makes RNA makes protein. Simply, it means that flow of information occurs in a strictly unidirectional manner from DNA to protein via well described processes of transcription and translation. Science does not accept any dogma and within two decades of publication of central dogma it was partially reversed by discovery of "RNA dependent DNA polymerase" or "Reverse transcriptase" . Till today the search for an enzyme which can catalyze the reverse translation of protein to polynucleotides proved fruitless. However, certain evidences point to possible existence of this type of enzyme. This paper tries to present a cogent argument from existing literature that such type of an enzyme, far from being conceptually heretic may in fact exist.

KEYWORDS:

Models, Genetic; Proteins/GE; Translation, Genetic; Transcription, Genetic; Scrapie/GE; Molecular Biology; Enzyme Activation; Transferases/GE; Human

References: 21

Record Identifier: NI201194

 Sorry the write up above is Directed to Prof Buckley who responded to Prof Laham ,s question.

Dear Akanjaksha Gosh,

it is heartening to hear from you. It seems we have encountered the same dogmatic dismissal for our belief in the process of reverse translation. By the way in 1976 that is what I originally proposed for my doctoral dissertation. Apart from the experimental evidence available back then that I offered to back up my theory I proposed novel experiments that would confirm its existence.

Since then the discovery of antisense RNA has reinforce my belie in such an enzymatic activity. It would be precisely the product of a reverse translatase that would "read" a novel antigen and would elaborate an RNA segment that codes for polypeptide that would fit the reactive site of the antigen like a glove for a hand. If that RNA segment is now incorporated by reverse transcriptase into the hyper variable section of an antibody gene, then you can have production of antibodies to that antigen. No need to store myriads of genes for antigens that did not exist when our somatic germ line was being established.

Your idea of reverse translation playing a central role in prions is I think genial. There is no way the central dogma can fully explain the idea of an "infectious

protein". Reverse translation would a the most plausible and simple explanation for the propagation of prions. I would appreciate a link to your 1999 paper

Sorry, I don't think it is plausible, because antibodies are not just against protein antigens. Antigens can be polysaccharides, lipids, nucleic acids, or even inorganic compounds, and they won't be converted to any RNAs you hypothesized. So I don't consider that reverse translation is the way how it works. The production of random and spontaneous diversity of antibodies is enough to deal with any antigens.

Indeed an epitope is a receptor structure that can be a combination of amino acid sequences, polysaccharides, fatty acids or combinations there of or as you point out inorganic structure synthesized in the lab.

it was these considerations that led me to believe that it made no sense at all that the genetic information to make antibodies to such structures are part of our established germ line. There would be no natural selective pressure to code for antibodies to antigens that did not exist, especially synthetic ones we regularly construct in the laboratory.

Hence I hypothesized back in the 70s that the evolution of an enzyme system capable of ‘reading an epitope’ and assembling the nucleic acid sequence, a form of antisence RNA that would code the hyper-variable site of an antibody that would bind to the antigen would be the most economic way evolution would give us this ability. And in a previous answer I site the experimental evidence that existed back then for that hypothesis.

Storing useless information to make antibodies to non existent antigens in our somatic germ line does not make evolutionary sense.