Preferential use of DH reading frame 2 alters B cell development and antigen-specific antibody production

Robert L. Schelonka, Michael Zemlin, Ryoki Kobayashi, Gregory C. Ippolito, Yingxin Zhuang, G. Larry Gartland, Alex Szalai, Kohtaro Fujihashi, Klaus Rajewsky, Harry W. Schroeder

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20 Scopus citations

Abstract

All jawed vertebrates limit use of DH reading frames (RFs) that are enriched for hydrophobic amino acids. In BALB/c mice, DFL16.1 RF2 encodes valine and isoleucine. To test whether increased use of RF2 affects B cell function, we examined B cell development and Ab production in mice with an IgH allele (ΔD-DμFS) limited to use of a single, frameshifted DFL61.1 gene segment. We compared the results of these studies to wild-type mice, as well as those previously obtained in mice limited to use of either a single normal DH or a single inverted DH that forces use of arginine in CDR-H3. All three of the mouse strains limited to a single DH produced fewer immature B cells than wild type. However, whereas mice limited to a single normal DH achieved normal B cell numbers in the periphery, mice forced to preferentially use RF2 had reduced numbers of mature B cells in the spleen and bone marrow, mirroring the pattern previously observed in mice enriched for charged CDR-H3s. There were two exceptions. B cells in the mice using RF2 normally populated the marginal zone and peritoneal cavity, whereas mice using inverted RF1 had increased numbers of marginal zone B cells and decreased numbers of B1a cells. When challenged with several T-dependent or T-independent Ags, Ag-specific Ab titers in the mice forced to use RF2 were altered. These findings indicate that B cell development and Ag-specific Ab production can be heavily influenced by the global amino acid content of the CDR-H3 repertoire.

Original languageEnglish (US)
Pages (from-to)8409-8415
Number of pages7
JournalJournal of Immunology
Volume181
Issue number12
DOIs
StatePublished - Dec 15 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Schelonka, R. L., Zemlin, M., Kobayashi, R., Ippolito, G. C., Zhuang, Y., Gartland, G. L., Szalai, A., Fujihashi, K., Rajewsky, K., & Schroeder, H. W. (2008). Preferential use of DH reading frame 2 alters B cell development and antigen-specific antibody production. Journal of Immunology, 181(12), 8409-8415. https://doi.org/10.4049/jimmunol.181.12.8409