A hypothesis on the role of immune RNA in antibody variability

The present hypothesis on the mechanism of antibody variability considers immune RNA (IMRNA) as a relatively independent “entity”. After having been transcribed in ontogenesis, as a result of stimulation of primordial multipotent “master cells” by primordial antigens, IMRNA behaves like an RNA virus genome. It controls only the variable part of immunoglobulin chains, proliferates and is transferred from committed to uncommitted cells, directly or using the macrophage as an “intermediate host”. During IMRNA proliferation “mutant” IMRNAs appear and control the synthesis of antibody variable regions of new specificity. The IMRNAs are reverse transcribed and inserted into DNA, chromosomal or extrachromosomal, near the gene controlling the constant part, and a complete CV gene is formed. The selective pressures which assure a relative constancy of IMRNA, so that only changes in the so-called hypervariable region are “tolerated” might be: the recognition by replicase, the insertion device, and the antigen-surface immunoglobulin-membrane receptor interaction. Arguments from immunology and from other fields of biology are brought in support at this hypothesis, and experimental approaches are suggested.