Assessment of a functional role of auto‐anti‐idiotypes in idiotype dominance

Abstract

We have used a well-defined idiotypic system, the cross-reactive idiotype of A strain (CRIA) (Ab1) idiotype generated in A/J mice injected with arsonate coupled to keyhole limpet hemocyanin (ARS-KLH), to determine the frequency of precursors for auto-anti-idiotypic antibodies (auto-Ab2) in naive and immunized A/J mice by limiting dilution analysis after polyclonal activation by lipopolysaccharide. In naive animals, the precursor frequencies of auto-Ab2 B cells were below the limit of sensitivity of the technique in the majority of A/J mice, and could be detected in only 20% of the animals. Upon immunization with ARS-KLH, a large increase in auto-Ab2 precursor frequency was observed. This shift in frequency was not found when A/J mice were injected with KLH alone, or when BALB/c mice, which do not express the CRIA idiotype, were injected with ARS-KLH. To study the functional role of the auto-Ab2 B cells, we injected neonatal A/J mice with polyclonal rabbit Ab3 antibodies directed against a recurrent idiotype of auto-Ab2. Thereafter, these mice were injected with ARS-KLH. Although the anti-arsonate response level was normal, the CRIA Ab1 expression was reduced tenfold. Thus, the suppression of auto-Ab2 affects Ab1 dominance. We further show that the presence of maternal Ab1 can strongly modify the immune response of the offspring by inducing higher levels of the idiotype after immunization. Furthermore, IgM anti-arsonate antibodies were detected before immunization with antigen. From these data, we conclude that the affinity of antigen alone cannot explain the dominance of CRIA. Network selection is important in the shaping of the available repertoire.

Lamarckian inheritance by somatically acquired maternal IgG phenotypes

“…However, this is not the case. First, a maternal secondary immunization with the hapten 2-phenyl-oxazolone (phOx) induced IgM anti-phOx in non-immunized F1 mice [46], a finding that has been confirmed in another system [50]. Second, a tertiary anti-phOx response or the transfer of highly immune-maturated quaternary antiphOx mAbs induced a complete dysregulation of the clonal composition of the primary anti-phOx reponse in the offspring at an age when the transferred maternal antibodies had long disappeared [51].…”

Maternal transfer of antibodies in vertebrates: trans-generational effects on offspring immunity

“…Desowitz 1971;Lange et al 2002;Lemke et al 2003), (ii) the enhancement of offspring endogenous antibody responses was only through the maternal, and not the paternal, line (Cookson et al 1992; for an example in birds see Reid et al 2006), (iii) the positive effect of offspring antibody responses was not a result of matAb transferring the specific antigen to the neonate (Ono et al 1974;Sasaki et al 1977;Jarrett & Hall 1983;Roberts & Turner 1983, (iv) secondary Ab response levels can be reached in offspring after a first injection with an antigen to which their mother had been repeatedly exposed (Stern 1976;Okamoto et al 1989), and (v) the enhanced effect could even be detected in the F2 generation, i.e. only when their grandmother had been injected with the antigen (Lemke et al 1994;Ismail et al 1995;Lange et al 1999;Lundin et al 1999). proposed a mechanism for how matAb could play an instructive role in the development of the endogenous humoral immune system of the offspring.…”

B-CD8+T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody

“…P3 is a monoclonal antibody, generated in BALB/c mice [1], that has the unique ability to induce in a syngeneic model a strong anti-idiotypic response in the absence of adjuvant or carrier protein [5, 14], which is not a frequently observed phenomenon [6, 48–50]. P3 was originally selected due to its binding to N -glycolylated gangliosides, but it also recognizes other self-molecules like sulfatides [1].…”

“…The V H of P3 is a germline and belongs to the Q52 (VH2) gene family, which was previously observed in autoantibodies against gangliosides and frequently used by CD5 + B-1a lymphocytes [3, 4]. P3 mAb triggers a strong anti-idiotypic response in the syngeneic model, BALB/c mice, even in the absence of adjuvant or carrier protein [5], which is not a commonly observed phenomenon [6]. This high anti-P3 idiotype antibody response might be part of a protection mechanism to block self-reactive antibodies.…”