The CDR-H3 repertoire from TdT-deficient adult bone marrow is a close, but not exact, homologue of the CDR-H3 repertoire from perinatal liver

Robert L. Schelonka, Ivaylo I. Ivanov, Andre M. Vale, Ewa Szymanska, Michael Zemlin, G. Larry Gartland, Harry W. Schroeder

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Abstract

Compared with adult bone marrow (BM), the composition of the perinatal liver CDR-3 of the Ig H chain (CDR-H3) repertoire is marked by a paucity of N nucleotides and by enrichment for use of JH proximal DQ52 and D H proximal VH and JH gene segments. To test the extent to which these differences reflect limited perinatal TdT activity versus differences in the fetal/adult environment, we used the Hardy scheme to sort fractions B-F B lineage cells from TdT-deficient BALB/c adult BM. V H7183-containing VDJCμ transcripts from these cells were amplified, cloned, sequenced, and compared with transcripts from wild-type perinatal liver and adult BM. The pattern of VHDJH usage in TdT-deficient BM largely matched that of TdT-sufficient adult cells. What minor differences were detected in the pro-B cell stage tended to diminish with B cell maturation, suggesting strong environmental or Ag-driven pressure to achieve a specific range of VHDJH usage regardless of the extent of N nucleotide addition. However, although the patterns of V HDJH usage in the TdT-deficient B lineage cells paralleled that of wild-type adult cells, the length distribution, global amino acid composition, and charge distribution of the CDR-H3 repertoire proved to be a close, although not exact, homologue of the CDR-H3 repertoire first expressed by late pre-B cells in the TdT-insufficient perinatal liver. Thus, although differing in VH content, TdT-deficient mice appear to represent a good, although not perfect, model for testing the role of perinatal CDR-H3 limitations on late B cell development and Ab responses.

Original languageEnglish (US)
Pages (from-to)6075-6084
Number of pages10
JournalJournal of Immunology
Volume185
Issue number10
DOIs
StatePublished - Nov 15 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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