Idiotype profile of an immune response. I. Contrasts in idiotypic dominance between primary and secondary responses and between IgM and IgG plaque- forming cells

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

Section: Serum From Germ-free Mice Has Decreased Amounts Of Id-460 Tmentioning

confidence: 75%

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.

Dzierzak¹,

Janeway²

1981

“…Antigens and hnmunization. ABA-KLH and ABA-CGG were prepared as described (15). ABA-Brucella was prepared according to Lucas and Henry (14), ie., by direct diazotization.…”

mentioning

confidence: 99%

“…Hemolytic Plaque Assay. The procedure for the plaque assay (15) was modified so that all antisera (anti-IdX, anti-IgM, or anti-IgG) and C, were added directly to the agar. The conjugation of target erythrocytes with the ABA-HB-imidoester was altered from the protocol of Isakson et al (19) as follows: (a) the concentration of RC in the haptenating mixture was 1/2.5 rather than 1/5; (b) the haptenation mixture was rocked for no more than 13 h; and (c) horse-or goat-RC were substituted for sheep-RC.…”

mentioning

confidence: 99%

Idiotype profile of an immune response. II. Reversal of the relative dominance of major and minor cross-reactive idiotypes in arsonate-specific T-independent responses.

Conger¹,

Lamoyi²,

Lewis³

et al. 1983

The antibody (Ab) l response of A/J mice to the p-azobenzenearsonate (ABA) hapten includes a substantial cross-reactive idiotypic (CRI or IdX) component (1). Serological (2) and amino acid sequence (3-5) studies on ABA-specific monoclonal Abs (mAb or HP) produced by hybridomas (derived using A/J ABAhyperimmune splenocytes) have indicated that all the HP examined are unique. However, CRI + HP can be shown to share one or more conserved IdX determinant(s) (6). Despite the microheterogeneity of the family of molecules bearing the major CRI, it appears that the heavy chain variable (VH), and probably the light chain variable (VL) regions are each encoded by a single germline gene that undergoes somatic variation (7,8). Recently, Milner and Capra (9) showed that the available N-terminal VH sequences could be classed into three distinct VH homology families, which might be termed: (a) the CRIA group (prototypes HP: R16.7, 93G7 [2], and 36-65 [4]); (b) the CRIc, family (prototypes: HP 92D5 [9] and 36-60 [10]); and, (c) the 96B8 family, which has not previously been serologically detected as a distinct IdX entity in the Ab response. It seems likely that these homology families result from the expression of at least three different Vu genes present in the strain A germline.A comparable complexity was recently demonstrated by Brown et al. (11) to exist at the serological level among induced anti-ABA Abs of A/J mice. Utilization of an anti-Id serum, prepared against HP R 16.7, which had previously been shown to bear virtually all of the major CRI determinants found among induced

“…T 15-specific suppressor T cells have also been found to be operating in the T 15positive antiphosphocholine response (37). Idiotype regulation of the transiently dominant CRI-positive antiarsonate response has also been observed (40) and appears to involve a ThId specific for CRI (41). Furthermore, immunization with a monoclonal anti-CRI antibody (AD8) has suggested a regulatory idiotypic connectance between CRI-positive, arsonate binding and CRI-positive, nonarsonate-binding antibody populations (14).…”

Section: Discussionmentioning

confidence: 99%

Non-dinitrophenyl-binding immunoglobulin that bears a dominant idiotype (Id460) associated with antidinitrophenyl antibody is specific for an antigen on Pasteurella pneumotropica.

Marion¹,

Dzierzak²,

Lee³

et al. 1984

We have previously described an idiotype (Id460) that transiently dominates anti-2,4-dinitrophenyl (DNP) antibody responses of mice that possess the appropriate Igh-V and V kappa genotypes. Normal serum has significant levels of Id460 that does not bind DNP, and hybridomas derived from spleen cell fusions that produce monoclonal antibodies with these characteristics have been generated. Many of these monoclonal, Id460-positive antibodies bind the opportunistic mouse pathogen Pasteurella pneumotropica. P. pneumotropica induces a marked increase in serum Id460 titers without significantly increasing serum anti-DNP titers. Both normal serum and P. pneumotropica-induced Ig460-positive immunoglobulin specifically bind to P. pneumotropica. These results suggest that the normal serum Id460-positive immunoglobulin is induced by environmentally encountered antigens on P. pneumotropica. We propose that this naturally occurring Id460 activates antiidiotypic regulatory cells that in turn promote production of Id460-positive anti-DNP antibody following DNP-ovalbumin immunization. These data are compatible with those obtained in several other idiotypic systems that suggest that dominant idiotypes may be associated with antibodies that have been evolutionarily selected for expression because of their specificity for antigens on environmentally encountered pathogens.