antibodyNaturally occurring antibodies, many of them preformed IgM, are vanguards of humoral immune defense. Hence, in chronic immune complex diseases, IgM do play a minor role the major part being taken over by IgG with their four subclasses IgG1, IgG2, IgG3 & IgG4. In this network, the epitope specificity is not the only criterion, but also the way it is presented to the antigen-recognizing apparatus: the surrounding of the epitope.

The epitope might be small, low-molecular weight, soluble thus without surrounding, or is fixed to a cell surface with an environment, a so called paratope. Antigenic enhancers, i.e. adjuvants and other wheels in the apparatus of the cellular immunity, e.g.monocytes/macrophages, dendritic cells, as well as T- B-and B1 cells. The CD11b+ human B1 cell subpopulation stimulates T cells and seems to be expanded in lupus.

In contrast to T-cell independent antigens, B-lymphocytes use for their response instruction by T—helper cells (CD4 cells) to achieve their antibody synthesis rate at a rate, if necessary of 2000 antibody molecules per second per cell. This performance is rewarded by the longest half-life of a serum protein known: IgG molecules if they are not suicidally used for immediate antigen removal live 21 days (subclass IgG3: 7 days), which is longer than the 19 days half-life time of albumin.

Thanks to nanontechnology, crystallography and proteomics the conviction grows, that it is the fine structure of the partners (not only amino acid sequence but also 3D-configuration, carbohydrate substitution, isoelectric points) which decides on ultimate properties of immune complexes conveyed by the complementarity determining regions (CDR) on the Fab recognition site of the Ig molecule. The vitreous water electron cryomicroscopy provides further insights (Nobel Prize in Chemistry 2017, University of Lausanne, Switzerland,  through the work of Jacques Dubochet).

Influence of some amino acids, like tyrosin, might prevail. Immune complexes are a normal phenomenon serving to remove antigen – however, if they last and remain detectable in peripheral blood or in tissues, they express underlying pathology. Their impact on components of innate immunity is as yet ill known.