title: Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production.
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 D(H) RF1-encoded tyrosine and glycine in regulating CDR-H3 content and potentially influencing B cell function, we created mice limited to a single D(H) 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 D(H) RF1 alters CDR-H3 content and impairs B cell development and antibody production.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, SHEL 401, Birmingham, AL 35294, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Ippolito
authors.forename: Robert L
authors.initials: RL
authors.lastname: Schelonka
authors.forename: Michael
authors.initials: M
authors.lastname: Zemlin
authors.forename: Ivaylo I
authors.initials: II
authors.lastname: Ivanov
authors.forename: Ryoki
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Cosima
authors.initials: C
authors.lastname: Zemlin
authors.forename: G Larry
authors.initials: GL
authors.lastname: Gartland
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.forename: Jukka
authors.initials: J
authors.lastname: Pelkonen
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
authors.forename: Harry W
authors.initials: HW
authors.lastname: Schroeder
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data
chemical_list: D000596:Amino Acids; D007143:Immunoglobulin Heavy Chains