Ontogeny of proteolytic immunity: IgM serine proteases.
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.
Planque
Stephanie
S
Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School, Houston, Texas 77030, USA.
Bangale
Yogesh
Y
Song
Xiao-Tong
XT
Karle
Sangeeta
S
Taguchi
Hiroaki
H
Poindexter
Brian
B
Bick
Roger
R
Edmundson
Allen
A
Nishiyama
Yasuhiro
Y
Paul
Sudhir
S
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
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