title: Ontogeny of proteolytic immunity: IgM serine proteases.
abstract: We report the chemical activity of immunoglobulin micro and kappa/lambda subunits expressed on the surface of B cells and in secreted IgM antibodies (Abs) found in the preimmune repertoire. Most of the nucleophilic reactivity of B cells measured by formation of covalent adducts of a hapten amidino phosphonate diester was attributed to micro and kappa/lambda subunits of the B cell receptor. Secreted IgM Abs displayed superior nucleophilic reactivity than IgG Abs. IgM Abs catalyzed the cleavage of model peptide substrates at rates up to 344-fold greater than IgG Abs. Catalytic activities were observed in polyclonal IgM Abs from immunologically naïve mice and humans without immunological disease, as well as monoclonal IgM Abs to unrelated antigens. Comparison of several IgM Abs indicated divergent activity levels and substrate preferences, with the common requirement of a basic residue flanking the cleavage site. Fab fragments of a monoclonal IgM Ab expressed catalytic activity, confirming the V domain location of the catalytic site. The catalytic reaction was inhibited by the covalently reactive hapten probe and diisopropylfluorophosphate, suggesting a serine protease-like mechanism. These observations indicate the existence of serine protease-like BCRs and secreted IgM Abs as innate immunity components with potential roles in B cell development and Ab effector functions.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School, Houston, Texas 77030, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Planque
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Bangale
authors.forename: Xiao-Tong
authors.initials: XT
authors.lastname: Song
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Karle
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taguchi
authors.forename: Brian
authors.initials: B
authors.lastname: Poindexter
authors.forename: Roger
authors.initials: R
authors.lastname: Bick
authors.forename: Allen
authors.initials: A
authors.lastname: Edmundson
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishiyama
authors.forename: Sudhir
authors.initials: S
authors.lastname: Paul
mesh_terms: D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002384:Catalysis; D005260:Female; D006241:Haptens / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology* / Q000378:metabolism*; D007145:Immunoglobulin kappa-Chains / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000276:immunology; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D012697:Serine Endopeptidases / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology
chemical_list: D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D007148:Immunoglobulin mu-Chains; D012697:Serine Endopeptidases