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

Academic Article

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 © The Rockefeller University Press.
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    Digital Object Identifier (doi)

    Author List

  • Ippolito GC; Schelonka RL; Zemlin M; Ivanov II; Kobayashi R; Zemlin C; Gartland GL; Nitschke L; Pelkonen J; Fujihashi K
  • Start Page

  • 1567
  • End Page

  • 1578
  • Volume

  • 203
  • Issue

  • 6