Role of group A streptococcal IgG Fc-receptor in induction of anti-IgG by immunization in the rabbit

Abstract

Previous work has demonstrated that streptococcal IgG Fc‐receptors (FcR) may trigger production of anti‐IgG after immunization of rabbits with group A streptococci. This effect seemed dependent on in vitro binding of IgG, derived from the growth medium, to the vaccine strains. In the experiments presented here, IgG was eluted from streptococcal strains to be used for immunization of rabbits by 1 M KSCN and washing, a treatment which did not affect the capacity of the strains to bind newly added IgG. Using two IgG FcR‐positive group A streptococcal strains (M‐types 1 and 22) for intravenous immunization, anti‐IgG was found in the sera of 26 out of 28 rabbits, examined 8 weeks after immunization. In contrast, anti‐IgG was not induced in 16 rabbits receiving either group A, type T27 or group B, type Ia streptococci both of which lack surface FcR activity. Finally, immunization with purified streptococcal IgG FcR (0.35 mg, given subcutaneously combined with Freund's complete adjuvant and two weeks later intraconjunctivally without adjuvant) also induced anti‐IgG. In all rabbits, anti‐human rather than anti‐rabbit IgG was detected. It is proposed that in vivo interaction between the bacterial FcR and rabbit IgG, resulting in conformation changes in IgG, is a prerequisite for the induction of anti‐IgG. Thus, streptococcal triggering of anti‐IgG, ascribable to IgG Fc‐receptor activity and not requiring presence of foreign IgG, has been demonstrated in the rabbit.

Pathogenesis of Group A Streptococcal Infections

“…Totolian, Burova, Schalen, and colleagues report in several studies that Fc receptor-positive streptococci induce the production of anti-IgG antibodies, which deposit in heart and kidney tissues and may trigger renal or myocardial damage (85)(86)(87). Streptococcal strains which did not contain immunoglobulin-binding proteins on the surface did not produce tissue damage.…”

Immune complex binding Streptococcus pyogenes type M12/emm12 in experimental glomerulonephritis

“…Tetanus–anti-tetanus (TAT) complexes were constructed from tetanus toxoid (SBL Vaccine) and human anti-tetanus IgG (Tetagam P, Behringwerke); the toxoid was radiolabelled with 125 I using Iodo-beads (Pierce Chemicals) according to the manufacturers’ instructions; optimal conditions for the radiobinding assay proved to be an Ab : Ag molar ratio 1 : 1, and use of TBS buffer at pH 6.0. Binding of radiolabelled, monomeric commercial IgG, in TBS at pH 8.0, was tested as described (Burova et al , 1989).…”

“…Female Chinchilla rabbits weighing 2.5–3.0 kg, obtained from the animal nursery ‘Rappolovo’ (St-Petersburg), were used. Selected GAS strains were tested in a previously described rabbit model (Burova et al , 2003); in brief, strains were grown aerobically in Todd–Hewitt broth (THB) overnight, heat-killed, treated with 1 M KSCN, and washed six times in PBS in order to remove any bound IgG (Burova et al , 1989). Rabbits were injected with streptococci in 1 ml PBS (10 9 c.f.u.…”

Purified Igg F C-Binding Proteins From M22 Group a Streptococcus Are Able to Induce Experimental Glomerulonephritis

“…Было показано, что IgG Fc-связывающие белки являются индукто-рами, способными вызывать продукцию анти-IgG [9]. Анти-IgG и циркулирующие иммунные комплексы IgG-анти-IgG либо агрегированные IgG должны обладать способностью отклады-ваться на базальной мембране клубочка, приво-дя в конечном итоге к иммунному воспалению и, как следствие, -к деструктивно-дегенератив-ным изменениям в клубочках.…”

“…Взаимодействие стрептококков с таким широким кругом белков крови не может пройти для организма-хозяина бесследно. Одним из важных последствий служит накопление анти-IgG-антител, приводящее к формированию в вы-сокой концентрации циркулирующих иммунных комплексов типа IgG -анти-IgG [8,9].…”