Autologous anti‐idiotypic antibody response is regulated by the level of circulating complementary idiotype

Abstract

SUMMARYBALB/c mice injected with lyophilized vaccine from Streptococcus pneumoniae R36a (Pn) predominantly responded with antibody molecules the vast majority of which expressed the public idiotype T15 and were directed to the immunodominant epitope phosphorylcholine (PC). However, after a single immunization with Pn vaccine young (3-month-old) BALB/c mice did not produce any specific anti-T15 antibody response. In contrast, young D1.LP mice were able to mount a specific anti-T15 response upon primary immunization with pneumococcal vaccine. The anti-PC response in the two mouse strains differed in that the proportion of antibody molecules that expressed the T15 idiotype for Pn-primed D1.LP mice showed a smaller proportion of PC-specific antibody expressing the T15 idiotype. Neonatal injection of anti-T15 monoclonal antibodies led to a long-term suppression of the PC-specific T15 B-cell clones but at young/adult age these mice maintained the ability to produce a normal amount of PC-specific antibody. Interestingly, the idiotypically-suppressed BALB/c mice mounted a significant anti-T15 response during the primary response to Pn. We interpreted these data as showing that the level of circulating idiotype may regulate the production of the complementary antiidiotypic antibody. In addition, in vitro experiments demonstrated that the lack of the anti-T15 response during primary antibody response in BALB/c mice is probably because of a state of tolerance that is regulated by T cells.

Low doses of IgG from atopic individuals can modulatein vitroIFN-γ production by human intra-thymic TCD4 and TCD8 cells: An IVIg comparative approach

“…We used this cell culture model to elucidate the direct effect of interactions between soluble IgG and cell populations in the human thymus. In this context, 4 main interactions can occur: I-IgG antibodies can idiotypically interact with membrane clonal receptors expressed by immature lymphocytes, [26][27][28][29] with the Fab regions of IgG being responsible for mediating this effect; II-IgG can interact via FcgR receptors expressed on B cells and possibly on thymic dendritic cells (tDCs) and macrophages, [30][31][32] with the Fc regions of IgG playing a pivotal role; III-IgG can permeate the membrane and mediate cytoplasmic interactions, 25 with the diversity of the Fab regions of IgG being responsible for mediating these interactions; and IV-IgG can be processed and presented by antigen-presenting cells (including tDCs and B cells) in the context of MHC molecules for recognition by clonal receptors on immature T cells, 33,34 with both Fc-and Fab-derived peptides of IgG being involved.…”

Integrating immunity: The immunculus and self-reactivity

“…Long-term tuning of selected clones of T-and B-lymphocytes of newborn animals under the influences of exogenously administered antibodies [22] may be considered as a rough model of immune imprinting. In any case immune imprinting clearly demonstrate a crucial feature: deviations of the maternal immunculus may ''imprint'' specifically on the immunculus of her offspring and thereby affect different organs in the child.…”

“…First, antibodies are able to carry specific signals for selective tuning of Tand B-lymphocytes of the same specificity [22,28,29]. Second, IgG autoantibodies of all specificities are always present in every compartment of the circulation [3].…”

Lamarckian inheritance by somatically acquired maternal IgG phenotypes

“…Hence, the pre-immune repertoire, as well as antigenactivated B and T cell clones, are subjected to internal Id regulation [23 -26]. The regulatory effect of Id -aId interactions is generally of short duration in adults, but long-lasting when induced during the neonatal period [27,28], and can even induce a permanent loss of the reactive Id [29] or enable the induction of normally silent clones [27,30]. Furthermore, neonatal Id suppression of multispecific IgM has profound consequences for a large part of the adult immune system [29,31].…”