Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production

Gregory C. Ippolito, Robert L. Schelonka, Michael Zemlin, Ivaylo I. Ivanov, Ryoki Kobayashi, Cosima Zemlin, G. Larry Gartland, Lars Nitschke, Jukka Pelkonen, Kohtaro Fujihashi, Klaus Rajewsky, Harry W. Schroeder

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Tyrosine and glycine constitute 40% of complementarity determining region 3 of the immunoglobulin heavy chain (CDR-H3), the center of the classic antigen-binding site. To assess the role of DH RF1-encoded tyrosine and glycine in regulating CDR-H3 content and potentially influencing B cell function, we created mice limited to a single DH encoding asparagine, histidine, and arginines in RF1. Tyrosine and glycine content in CDR-H3 was halved. Bone marrow and spleen mature B cell and peritoneal cavity B-1 cell numbers were also halved, whereas marginal zone B cell numbers increased. Serum immunoglobulin G subclass levels and antibody titers to T-dependent and T-independent antigens all declined. Thus, violation of the conserved preference for tyrosine and glycine in DH RF1 alters CDR-H3 content and impairs B cell development and antibody production. JEM

Original languageEnglish (US)
Pages (from-to)1567-1578
Number of pages12
JournalJournal of Experimental Medicine
Volume203
Issue number6
DOIs
StatePublished - Jun 12 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Ippolito, G. C., Schelonka, R. L., Zemlin, M., Ivanov, I. I., Kobayashi, R., Zemlin, C., Gartland, G. L., Nitschke, L., Pelkonen, J., Fujihashi, K., Rajewsky, K., & Schroeder, H. W. (2006). Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production. Journal of Experimental Medicine, 203(6), 1567-1578. https://doi.org/10.1084/jem.20052217