Genetic analysis of the maternally induced affinity enhancement in the non-Ox1 idiotypic antibody repertoire of the primary immune response to 2-phenyloxazolone

Scand J Immunol. 1999 Jan;49(1):55-66. doi: 10.1046/j.1365-3083.1999.00472.x.

Abstract

The early phases of ontogeny are decisive for the development of the B-cell repertoire. Here, we demonstrate that maternal tertiary immunization of BALB/c mice with 2-phenyloxazolone (phOx) caused a drastic alteration of the primary antigen-specific repertoire of the offspring. Maternal tertiary immunization or quaternary antibodies, which exhibited an extremely weak cross-reactivity with the major Ox1 idiotype (IdOx1), induced a change in the proportion of IdOx1/non-IdOx1 antiphOx antibodies in the F1 and F2 primary repertoire. The observed variability in the level of IdOx1 expression (10-90%) exceeded even the seemingly genetically based differences between various mouse strains. In comparison with the non-IdOx1 of control mice, half of the non-IdOx1 antibodies showed a 5-100-fold enhanced affinity. Sixty per cent of these antibodies exhibited an affinity identical to that of IdOx1 antibodies, which are normally of the highest affinity, while the remaining 40% exceeded even that of IdOx1 by a factor of 10. The non-IdOx1 were encoded by VH/VL genes and/or combinations thereof which are either new, hitherto unobserved in the antiphOx response, or typical of memory responses in normal mice. The significance of these data is discussed with respect to the possibility that maternal antibodies, which are acquired through multiple immune maturation processes, may have an epigenetic (non-Mendelian) inheritable potential for the offspring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Anti-Idiotypic / biosynthesis*
  • Antibodies, Anti-Idiotypic / blood
  • Antibodies, Anti-Idiotypic / genetics
  • Antibody Affinity / genetics*
  • Base Sequence
  • Female
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Gene Rearrangement, B-Lymphocyte, Light Chain
  • Haptens / administration & dosage
  • Haptens / genetics
  • Haptens / immunology*
  • Immune Sera / analysis
  • Immunization
  • Immunoglobulin Heavy Chains / biosynthesis
  • Immunoglobulin Heavy Chains / blood
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Light Chains / biosynthesis
  • Immunoglobulin Light Chains / blood
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Variable Region / biosynthesis
  • Immunoglobulin Variable Region / blood
  • Immunoglobulin Variable Region / genetics
  • Maternal-Fetal Exchange / genetics
  • Maternal-Fetal Exchange / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Oxazolone / administration & dosage
  • Oxazolone / analogs & derivatives*
  • Oxazolone / immunology
  • Pregnancy

Substances

  • Antibodies, Anti-Idiotypic
  • Haptens
  • Immune Sera
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • 2-phenyloxazolone
  • Oxazolone

Associated data

  • GENBANK/AF150879
  • GENBANK/AF152340