Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. III. Detection of Id-460 in normal serum that does not bind dinitrophenyl.

Abstract

In Jerne's network theory (1), the immune system is envisaged as a web of interactions between immunoglobulin variable domains. In this schema, regulation (amplification and suppression) of the immune response occurs when anti-idiotype antibody (Ab2) reacts with idiotypes (Ab 1) induced by foreign antigenic stimulation. Ab2 also induces and reacts with a nonspecific parallel set of antibody (Ab3)-bearing idiotypes shared with Abl but not binding the immunizing antigen. Induction, amplification, and suppression of the immune response thus result from the regulatory network of idiotype-anti-idiotype interactions.To probe the importance of idiotypic regulation on the heterogeneous response to the hapten 2,4-dinitrophenyl (DNP), 1 we have studied the expression of an idiotype (Id-460) associated with the DNP-binding, BALB/c IgA,~ myeloma protein MOPC 460 during in vivo anti-DNP antibody responses (2). Id-460 is expressed in a transiently dominant manner both in serum and by splenic anti-DNP plaque-forming cells; dominant expression occurs early in the secondary in vivo response to DNPovalbumin (OVA) in mice having Igh-V a and able to express light chains of the V~I group (2, 3). We have previously demonstrated (4-6) the existence of two helper T cells (Th) acting synergistically early in the course of in vivo secondary anti-DNP responses. One of these two Th was shown by adoptive transfer experiments to be lacking in T cells derived from mice treated from birth with anti-/~ antibody (7). This suggested the need for immunoglobulin (Ig) in the differentiation of this T cell. This cell was also shown to be Lyt-l+,2 -and antigen specific (8). We have proposed that this cell recognizes idiotype and is responsible for the dominant expression of Id-460 in the anti-DNP response. This is consistent with findings of Ig-recognizing T cells in other major idiotypic systems (9-11). However, in these other systems idiotype is associated with antibody directed against bacterial antigens. If inherited idiotypes are primarily directed at common environmental antigens and are important in resistance to common pathogens (12), the existence of an inherited, dominant idiotype associated

Normal mice express idiotypes related to autoantibody idiotypes of lupus mice

“…The H130 idiotypic family seems, therefore, to encompass a group of antibodies, the majority of which do not bind to DNA. There are other examples of idiotypes that are shared by antibodies with different antigen-binding specificities (18)(19)(20)(21). This observation conforms with Jerne's (22) network hypothesis, which postulates regulation of the immune response by anti-idiotypic antibody (Ab2) reacting with idiotypes (Abl) that are induced by antigenic stimulation.…”

“…The DNA-binding components of the three idiotype families analyzed here may belong to the parallel set (Ab3) that shares idiotypes with antibodies that are not directed primarily against DNA. Dzierak and Janeway (21) have pointed to the remarkable fact that most inherited dominant idiotypes are directed against bacterial antigens: T15 is anti-phosphocholine and protects mice against pneumococcal infection (23); A5A is anti-streptococcal group A carbohydrate; MOPC 104E is anti-dextran; and UPC-10 is anti-levan (21). The H130-, H102-, and H43-related idiotypes that genetically different strains of mice can express may also be directed primarily against certain common pathogens.…”

Idiotype connectance in the immune system. I. Expression of a cross-reactive idiotype on induced anti-p-azophenylarsonate antibodies and on endogenous antibodies not specific for arsonate.

“…Here the antiidiotype would be stimulating a de novo response. The possible connection between endogenous immune responses and idiotype dominance in induced antihapten responses has been made before in other systems (8,15). The experiments shown above lend further credence to this notion.…”

“…Lymphocyte clones that are individually specific for structurally dissimilar epitopes can be functionally connected through shared idiotypy. Although idiotype sharing between antibodies binding to different epitopes was first reported in 1971 by Oudin and Cazenave (1), followed by repeated confirmations at the immunochemical level (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), the biological consequences of such idiotype sharing have remained relatively uncharted. By incorporating unspecific parallel sets into the network hypothesis, Jerne (13) predicted the importance of shared idiotypy between lymphocyte clones specific for non-cross-reactive epitopes as a means of joining otherwise unconnected immune responses at the regulatory level.…”

ABPC 48 cross-reactive idiotopes in BALB/c mice. Natural and levan-induced expression.

“…The absence of sensitive and specific assays imposed as a rule to consider preimmune sera activities as background. However, several attempts (11)(12)(13)(14) have been made to define natural idiotypic activities by means of polyclonal antiidiotypic antibodies. In such systems, the immunoglobulins that are detected may correspond to various structures.…”