Recirculating bone marrow B cells in C57BL/6 mice are more tolerant of highly hydrophobic and highly charged CDR-H3s than those in BALB/c mice

Mohamed Khass, Kevin Buckley, Pratibha Kapoor, Robert L. Schelonka, Leticia S. Watkins, Yingxin Zhuang, Harry W. Schroeder

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

To test whether mechanisms controlling the range of diversity of the developing antibody repertoire in C57BL/6 mice (IgHb) operate similarly to those identified in BALB/c mice (IgHa), we compared the sequences of VH7183-containing H-chain transcripts from sorted adult bone marrow C57BL/6 B-cell subsets with those previously obtained from BALB/c mice. Patterns of VDJ gene segment utilization and CDR-H3 amino acid composition, charge, and average length in C57BL/6 pro-B cells were similar, although not identical, to BALB/c pro-B cells. However, C57BL/6 mature, recirculating B cells failed to demonstrate the reduction in the use of VH81X and the narrowing in the range of variance of CDR-H3 hydrophobicity that characterizes B-cell maturation in BALB/c mice. To further test the ability of the C57BL/6 strain to discard B cells expressing highly charged CDR-H3s, we introduced a mutant IgHa DH allele that forces use of arginine, asparagine, and histidine. Unlike BALB/c mice, C57BL/6 mice congenic for the charged DH maintained normal numbers of mature, recirculating B cells that were enriched for charged CDR-H3s. Together these findings indicate that the mature C57BL/6 B-cell pool permits expression of immunoglobulins with antigen-binding sites that are typically discarded during late-stage bone marrow B-cell development in BALB/c mice.

Original languageEnglish (US)
Pages (from-to)629-640
Number of pages12
JournalEuropean Journal of Immunology
Volume43
Issue number3
DOIs
StatePublished - Mar 1 2013

Keywords

  • Antibodies
  • B cells
  • Repertoire development
  • Rodent

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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