Contribution of light chain rearrangement in peripheral B cells to the generation of high-affinity antibodies

Masaki Magari, Takashi Sawatari, Yohei Kawano, Marilia Cascalho, Matthias Wabl, Naoki Kanayama, Masaki Hikida, Hitoshi Ohmori

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Recently, peripheral B cells have been shown to undergo secondary V(D)J rearrangement of immunoglobulin genes, but the physiological role of this event has not been fully elucidated. To investigate whether rearrangement of L chain genes in the periphery is involved in the generation of high-affinity antibodies (Ab), we used the 17.2.25 rearranged VHDJH gene (VHT)-knockin mouse whose B cell diversity is limited due to the expression of the site-directed transgene. Immunization of the mouse with p-nitrophenylacetyl (pNP)-conjugated chicken γ-globulin preferentially led to the production of anti-pNP IgG Ab comprised of non-VHT-encoded H chains and λ chains. λ+ IgG constituted a majority of high-affinity Ab to this hapten. RAG-2 mRNA and the recombination signal sequence break of the λ1 gene increased in the draining lymph node of immunized mice, but not of nonimmunized animals. There was a close correlation between the levels of these parameters implicating λ gene rearrangement and the production of λ+ high-affinity anti-pNP IgG. These observations were reproduced in RAG-1-deficient mice that were reconstituted with the spleen cells of the knockin mouse. Thus, our findings suggest that L chain rearrangement that occurs in the periphery can contribute to affinity maturation of Ab.

Original languageEnglish
Pages (from-to)957-966
Number of pages10
JournalEuropean Journal of Immunology
Volume32
Issue number4
DOIs
Publication statusPublished - May 4 2002

Keywords

  • Affinity maturation
  • Antibody
  • Lymph node
  • RAG
  • V(D)J recombination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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