Jun 7, 2006

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

The Journal of Experimental Medicine
Gregory C IppolitoHarry W Schroeder

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.

Mentioned in this Paper

Asparagine
Histidine
Immunoglobulin Activity
Mice, Inbred BALB C
Spleen
Amino Acids, I.V. solution additive
Bone Marrow
Antibody Titer Measurement
Marginal Zone
Cell Count

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