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

Authors :
G. Larry Gartland
Ivaylo I. Ivanov
Gregory C. Ippolito
Cosima Zemlin
Robert L. Schelonka
Klaus Rajewsky
Jukka Pelkonen
Kohtaro Fujihashi
Ryoki Kobayashi
Michael Zemlin
Lars Nitschke
Harry W. Schroeder
Source :
The Journal of Experimental Medicine
Publication Year :
2006
Publisher :
Rockefeller University Press, 2006.

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.

Details

ISSN :
15409538 and 00221007
Volume :
203
Database :
OpenAIRE
Journal :
Journal of Experimental Medicine
Accession number :
edsair.doi.dedup.....57fb22635a8063c3d892ede27755252d
Full Text :
https://doi.org/10.1084/jem.20052217