A single DH gene segment creates its own unique CDR-H3 repertoire and is sufficient for B cell development and immune function

Robert L. Schelonka, Ivaylo I. Ivanov, David H. Jung, Gregory C. Ippolito, Lars Nitschke, Yingxin Zhuang, G. Larry Gartland, Jukka Pelkonen, Frederick W. Alt, Klaus Rajewsky, Harry W. Schroeder

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

To test the contribution of individual D gene segments to B cell development and function, we used gene targeting to create mice that contain only DFL16.1 in the DH locus. We term this D-limited IgH allele ΔD-DFL. Although the absolute number of IgM+IgD- B cells in the bone marrow was decreased, homozygous ΔD-DFL BALB/c mice contained normal numbers of IgM+IgD+ B cells in bone marrow and spleen and normal numbers of B1a, B1b, and B2 cells in the peritoneal cavity. Bone marrow IgM+IgD+ B cells express a CDR-H3 repertoire similar in length and amino acid composition to the DFL16.1 subset of the wild-type BALB/c repertoire but divergent from sequences that do not contain DFL16.1. This similarity in content is the product of both germline bias and somatic selection, especially in the transition to the mature IgM +IgD+ stage of development. Serum Ig concentrations and the humoral immune response to a T-dependent Ag ([4-hydroxy-3-nitrophenyl]acetyl hapten) were nearly identical to wild-type littermate controls. A greater variance in the immune response to the T-independent Ag (α(1→3)- dextran) was observed in ΔD-DFL homozygotes, with half of the mice exhibiting levels below the range exhibited by controls. Although limited to a repertoire specific to DFL16.1, the presence of a single DH gene segment of normal sequence was sufficient for development of normal numbers of mature B cells and for robust humoral immune function.

Original languageEnglish (US)
Pages (from-to)6624-6632
Number of pages9
JournalJournal of Immunology
Volume175
Issue number10
DOIs
StatePublished - Nov 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Schelonka, R. L., Ivanov, I. I., Jung, D. H., Ippolito, G. C., Nitschke, L., Zhuang, Y., Gartland, G. L., Pelkonen, J., Alt, F. W., Rajewsky, K., & Schroeder, H. W. (2005). A single DH gene segment creates its own unique CDR-H3 repertoire and is sufficient for B cell development and immune function. Journal of Immunology, 175(10), 6624-6632. https://doi.org/10.4049/jimmunol.175.10.6624