Suppression of Idiotypic Specificities in Adult Mice by Administration of Antiidiotypic Antibody

Hart, David A.; Wang, Ai-Lan; Pawlak, Laura L.; Nisonoff, Alfred

doi:10.1084/jem.135.6.1293

Cited by 251 publications

(101 citation statements)

References 15 publications

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“…This is a positive interaction similar to a proliferative response to antigen. Administration of anti-idiotypic antibodies can both enhance (Eichmann and Rajewsky, 1975;Vakil and Kearny, 1986;Bernabe et al, 1981) and suppress (Hardt et al, 1972;Eichmann, 1974;Vakil and Kearny, 1986) the idiotypic immune response. Because all populations are identical in our model, and because idiotypic are symmetric, we have no a priori basis to discriminate between stimulatory and inhibitory interactions.…”

Section: A New Networkmentioning

confidence: 99%

Memory but no suppression in low-dimensional symmetric idiotypic networks

Boer

Hogeweg

1989

Bltn Mathcal Biology

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We present a new symmetric model of the idiotypic immune network. The model specifies clones of B-lymphocytes and incorporates: (1) influx and decay of cells; (2) symmetric stimulatory and inhibitory idiotypic interactions; (3) an explicit affinity parameter (matrix); (4) external (i.e. nonidiotypic) antigens. Suppression is the dominant interaction, i.e. strong idiotypic interactions are always suppressive. This precludes reciprocal stimulation of large clones and thus infinite proliferation. Idiotypic interactions first evoke proliferation, this enlarges the clones, and may in turn evoke suppression. We investigate the effect ofidiotypic interactions on normal proliferaJtive immune responses to antigens (e.g. viruses).A 2-D, i.e. two clone, network has a maximum of three stable equilibria: the virgin state and two asymmetric immune states. The immune states only exist if the affinity of the idiotypic interaction is high enough. Stimulation with antigen leads to a switch from the virgin state to the corresponding immune state. The network therefore remembers antigens, i.e. it accounts for immunity/memory by switching beteen multiple stable states. 3-D systems have, depending on the affinities, 9 qualitatively different states. Most of these also account for memory by state switching.Our idiotypic network however fails to account for the control of proliferation, e.g. suppression of excessive proliferation. In symmetric networks, the proliferating clones suppress their anti-idiotypic suppressors long before the latter can suppress the former. The absence of proliferation control violates the general assumption that idiotypic interactions play an important role in immune regulation. We therefore test the robustness of these results by abandoning our assumption that proliferation occurs before suppression. We thus define an "escape from suppression" model, i.e. in the "virgin" state idiotypic interactions are now suppressive. This system erratically accounts for memory and never for suppression. We conclude that our "absence of suppression from idiotypic interactions" does not hinge upon our "proliferation before suppression" assumption.

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Section: A New Networkmentioning

confidence: 99%

Memory but no suppression in low-dimensional symmetric idiotypic networks

Boer

Hogeweg

1989

Bltn Mathcal Biology

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“…Jerne (15) suggested that an Id network maintains the homeostasis of the immune response. It was proposed that Id and anti-Id can manipulate cellular and humoral immunity (6,22). An anti-Id antibody bearing the internal image of external antigen has been demonstrated and used for the induction of specific immune response (10,18,19).…”

mentioning

confidence: 99%

“…An anti-Id antibody bearing the internal image of external antigen has been demonstrated and used for the induction of specific immune response (10,18,19). In various antigenic systems, the injection of Ab2 modified the production of Ab 1 expressing the corresponding Id (6,8,23). In some systems, preinjection with Ab2 specifically suppressed the production of the given Ab 1 (6,8).…”

mentioning

confidence: 99%

“…In the 1st method, idiotypic suppression was induced following the protocol originally described by Hart et al (6). As we reported that all of DBA/1J mice immunized with Rai-5 could produce anti-CH antibody expressing 1-5 Id (11) In the next experiment, the above four anti-1-5 Id mAbs were examined to determine whether these would recognize the same idiotope on 1-5 mAb.…”

mentioning

confidence: 99%

“…In various antigenic systems, the injection of Ab2 modified the production of Ab 1 expressing the corresponding Id (6,8,23). In some systems, preinjection with Ab2 specifically suppressed the production of the given Ab 1 (6,8). Arita et al reported that CIA in rats could be suppressed by anti-Id antisera against anti-CII antibodies (1).…”

mentioning

confidence: 99%

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Collagen‐Induced Arthritis Suppressed with Monoclonal Anti‐Idiotypic Antibody

Tarutani

1993

Microbiology and Immunology

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: In foregoing work, we identified at least 5 distinct epitopes on human type II collagen (CII), using 8 murine monoclonal antibodies (mAb) against human CII, and suggested that a species-nonspecific epitope on CII recognized by anti-CII mAb termed 1-5 is an arthritogenic epitope. We also found that antibody response against a selected epitope of human CII could be induced by immunization with rabbit anti-idiotypic (Id) antibody against anti-CII mAb. The author developed and characterized monoclonal anti-Id antibodies against 1-5 mAb recognizing a putative arthritogenic epitope. The author also investigated whether the anti-Id mAb could regulate antibody response directed against a selected epitope recognized by 1-5 mAb, and the induction of collagen-induced arthritis in DBA/1J mice. DBA/1J mice intravenously preinjected with anti-Id mAb to 1-5, did not produce anti-CII antibody expressing 1-5 Id upon immunization with human CII. Furthermore, as the development of collagen-induced arthritis (CIA) in DBA/ 1J mice pretreated with anti-Id mAb to 1-5 was significantly suppressed, anti-Id mAb will be a useful tool for studying the regulation of antibody response to a selected epitope. This study lends support to our hypothesis that the 1-5 epitope is an arthritogenic epitope.

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Monoclonal lupus autoantibodies

Rauch

Lafer

Andrzejewski

et al. 1982

Arthritis & Rheumatism

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The autoimmune syndrome o f systemic lupus erythema t o s u s (SLE) encompasses a d i v e r s i t y o f c l i n i c a l and immunological a b n o r t n a l i t i e s , some o f which remain as b a f f l i n g today as t h e y were twenty y e a r s ago. The d i s o r d e r should, we b e l i e v e , be regarded as a syndrome because i t may e i t h e r a r i s e spontaneously, e r u p t a f t e r exposure t o u l t r a v i o l e t l i g h t , o r develop d u r i n g t r e a tment w i t h a v a r i e t y o f drugs.I t can, moreover, v a r y i n c l i n i c a l s e v e r i t y from m i l d a r t h r a l g i a t o r a p i d l y p r o g r e s s i v e g l o m e r u l o n e p h r i t i s .A f e a t u r e commn t o a l l forms o f t h e l u p u s syndrome i s t h e presence o f a n t i b o d i e s t o one o r more c o n s t i t u e n t s o f t h e c e l l nucleus, i n c l u d i n g DNA ( e i t h e r s i n g l e strarlded DNA sDNA , double s t r a n d e d DNA dsDNA o r both), n u c l e op r o t e i n s , and h i s t o n e s . I n a d d i t i o n , o t h e r a n t i b o d i e s may a r i s e :autoimmune h e m o l y t i c anemia, thrombocytopenia, l u p u s a n t i c o a g u l a n t s , and b i o l o g i c a l l y f a l s e p o s i t i v e t e s t s f o r s y p h i l i s a r e common problems.The o r i g i n s o f l u p u s a u t o a n t i b o d i e s a r e unknown. Whether n u c l e i c a c i d s themselves p r o v i d e t h e immunizing s t i m u l u s remains e n i g m a t i c , e s p e c i a l l y because dsDNA i s a v e r y weak immunogen --even i n experimental a n i m a l s t h a t a r e g e n e t i c a l l y programmed t o produce anti-DNA a n t i b o d i e s spontaneously ( 1 ) . D e f i c i e n c i e s o f T lymphocyte f u n c t i o n , n o t a b l y t h o s e o f suppressor c e l l s , have been i m p l i c a t e d i n SLE (2). b u t t h e y l a c k t h e s p e c i f i c i t y t h a t corresponds t o t h e s p e c i f i c i t y o f l u p u s a u t o a n t i b o d i e s and t h e i r p r e d i l e c t i o n f o r n u c l e a r c o n s t i t u e n t s . Moreover, t h e presence o f i d e n t i c a l a b n o r m a l i t i e s i n some c l i n i c a l l y normal, s e r o n e g a t i v e r e l a t i v e s o f p a t i e n t s w i t h SLE ( 3 ) argues t h a t i m p a i r e d f u n c t i o n o f suppressor lymphocytes does n o t , by i t s e l f , i n s t i g a t e t h e p r o d u c t i o n o f l u p u s a u t o a n t i b o d i e s .Many o f t h e p u z z l i n g aspects o f SLE would be c l a r i f i e d by d e t a i l e d analyses o f t h e immunochemistry of l u p u s a u t o a n t i b o d i e s .Such work, however, has been hampered by t h e f o r m i d a b l e t e c h n i c a l problem o f separ a t i n g i n d i v i d u a l a n t l b o d i e s from t h e complex m i x t u r e of a n t i b o d i e s i n l u p u s serum. The i s o l a t i o n o f i n d i v idual a n t i b o d i e s i s e s s e n t i a l t o d i s t i n g u i s h t r u e speci f i c i t y from t h e c r o s s r e a c t i o n s o f m i x t u r e s o f...

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Suppression of Idiotypic Specificities in Adult Mice by Administration of Antiidiotypic Antibody

Cited by 251 publications

References 15 publications

Memory but no suppression in low-dimensional symmetric idiotypic networks

Memory but no suppression in low-dimensional symmetric idiotypic networks

Collagen‐Induced Arthritis Suppressed with Monoclonal Anti‐Idiotypic Antibody

Monoclonal lupus autoantibodies

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