The perinatal presence of antigen (p-azophenylarsonate) or anti-μ antibodies lead to the loss of the recurrent idiotype (CRI_A) in A/J mice

Abstract

The immune response of A/J mice against p-azophenylarsonate (Ars)-keyhole limpet hemocyanin (KLH) is characterized by the dominance, late in primary and during the secondary, of a recurrent idiotype called CRIA, encoded by a canonical combination of Ig gene segments. In this study, A/J mice were given Ars coupled to deaggregated human gamma globulins (dHGG) within 24 h after delivery. The offsprings from these mice were then exposed as adults to Ars-KLH. These animals developed an unusual immune response. The level of anti-Ars antibodies was nearly normal but a dramatic shift in repertoire was observed: the cross-reactive idiotype which is the hallmark of the anti-Ars response in A/J mice was completely absent. The idiotype could be recovered by injection of anti-idiotypic antibodies alone, with no need of lipopolysaccharide coupling. Therefore the presence of antigen at birth can lead to a strong perturbation of idiotype selection. Similar results were obtained with neonatal treatment using anti-IgM antibodies. After recovery of suppression, A/J mice can mount an anti-arsonate response of normal level but devoid of the dominant idiotype.

Distinct VH repertoires in primary and secondary B cell lymphocyte subsets in the preimmune repertoire of A/J mice: the CRI-A idiotype is preferentially associated with the HSAlow B cell subset

“…This would suggest that affinity alone cannot dictate dominance. In agreement our data suggest that idiotype dominance can be easily broken by various means, while the level of anti-arsonate antibodies is usually not affected [13][14][15][16].…”

“…The inactivation of autoanti-idiotypic precursor B cells in neonates [15] as well as the treatment at birth with antigen or anti-? antibodies [14] lead to the loss of CRI-A dominance, while the levels of anti-arsonate antibodies are normal.…”

Maternal provisions in type 1 diabetes: Evidence for both protective & pathogenic potential

“…It is known that anti-Id antibodies can be generated by the neonate in response to maternal IgG ( 180 ) or acquired from the mother ( 179 ). Several studies have demonstrated the ability of endogenous and maternally-delivered anti-Id antibodies to modify the B lymphocyte repertoire in neonatal mice, often resulting in suppression of the targeted B lymphocyte ( 181 – 183 ). Furthermore, there is evidence that T cell receptors (TCR) may also be a target for anti-Id antibody suppression in neonatal mice, resulting in early shaping of the T lymphocyte repertoire ( 184 ) ( Figure 3 ).…”

Relevance of the Materno-Fetal Interface for the Induction of Antigen-Specific Immune Tolerance

“…In such systems, the suppression of antibody responses was always reversible. Its recovery was associated with the expression of the same (151) or different idiotypic repertoires (152)(153)(154). For instance, the transfer of maternal anti-idiotypic IgGs directed against anti-phosphorylcholine (PC) antibodies skewed the repertoires of PC-specific B lymphocytes after immunization of the offspring with PC later in life (155).…”