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Somatic mutation in the neonatal mouse

C A Giorgetti1, J L Press

  • 1Brandeis University, Rosenstiel Research Center, Waltham, MA 02454, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|December 2, 1998
PubMed
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Neonatal mice can activate somatic mutation machinery, enabling B cells to diversify their immune repertoire soon after birth. This suggests early vaccination can lead to protective immunity in newborns.

Area of Science:

  • Immunology
  • Developmental Biology
  • Vaccinology

Background:

  • Adult immune repertoire diversification relies on mechanisms like somatic mutation for high-affinity memory B cell generation.
  • Neonatal mice lack certain adult immune diversification mechanisms, such as terminal deoxynucleotidyl transferase-dependent N region addition.
  • The capacity of neonatal mouse B cells to activate somatic mutation machinery remains unclear.

Purpose of the Study:

  • To investigate whether B cells in neonatal mice can activate somatic mutation.
  • To determine if somatic mutation machinery is functional in the early neonatal period.
  • To assess the potential for early vaccination to induce affinity maturation and protective immunity.

Main Methods:

  • Neonatal mice were immunized with specific antigen-protein complexes: poly(L-Tyr,L-Glu)-poly-D,L-Ala-poly-L-Lys/methylated BSA or (4-hydroxy-3-nitrophenyl)acetyl/chicken gamma-globulin.

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  • Heavy chain V(D)J rearrangements from immunized neonates were screened for mutations using temperature-melt hybridization and specific oligonucleotide probes.
  • Potential mutations were confirmed through sequence analysis.

    • Main Results:

    • Somatic mutations were detected in heavy chains of neonatal mice immunized with (4-hydroxy-3-nitrophenyl)acetyl coupled to chicken gamma-globulin, more so than with the other antigen.
    • Mutations were observed in heavy chains lacking N regions, indicating B cells from the fetal lineage can undergo somatic mutation.
    • Mutations were present in neonates immunized as early as 1-2 days after birth.

    Conclusions:

    • Neonatal mouse B cells possess the capability to activate somatic mutation machinery shortly after birth.
    • Somatic mutation allows for the diversification of a limited initial repertoire in neonates.
    • Early life vaccination has the potential to induce affinity maturation and establish protective immunity in neonates.