Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production.
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.
Ippolito
Gregory C
GC
Department of Microbiology, University of Alabama at Birmingham, SHEL 401, Birmingham, AL 35294, USA.
Schelonka
Robert L
RL
Zemlin
Michael
M
Ivanov
Ivaylo I
II
Kobayashi
Ryoki
R
Zemlin
Cosima
C
Gartland
G Larry
GL
Nitschke
Lars
L
Pelkonen
Jukka
J
Fujihashi
Kohtaro
K
Rajewsky
Klaus
K
Schroeder
Harry W
HW
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
D000596:Amino Acids; D007143:Immunoglobulin Heavy Chains