TY - JOUR
T1 - Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production
AU - Ippolito, Gregory C.
AU - Schelonka, Robert L.
AU - Zemlin, Michael
AU - Ivanov, Ivaylo I.
AU - Kobayashi, Ryoki
AU - Zemlin, Cosima
AU - Gartland, G. Larry
AU - Nitschke, Lars
AU - Pelkonen, Jukka
AU - Fujihashi, Kohtaro
AU - Rajewsky, Klaus
AU - Schroeder, Harry W.
PY - 2006/6/12
Y1 - 2006/6/12
N2 - 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
AB - 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
UR - http://www.scopus.com/inward/record.url?scp=33745053586&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745053586&partnerID=8YFLogxK
U2 - 10.1084/jem.20052217
DO - 10.1084/jem.20052217
M3 - Article
C2 - 16754718
AN - SCOPUS:33745053586
SN - 0022-1007
VL - 203
SP - 1567
EP - 1578
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -