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J. Biol. Chem., Vol. 279, Issue 14, 14024-14032, April 2, 2004

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Ontogeny of Proteolytic Immunity

IgM SERINE PROTEASES^*

Stephanie Planque, Yogesh Bangale, Xiao-Tong Song, Sangeeta Karle, Hiroaki Taguchi, Brian Poindexter, Roger Bick, Allen Edmundson, Yasuhiro Nishiyama, and Sudhir Paul

From the Chemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School, Houston, Texas 77030 and the Crystallography Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104

We report the chemical activity of immunoglobulin µ and / 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 µ and / 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.

Received for publication, November 5, 2003 , and in revised form, January 9, 2004.

^* This work was supported by National Institutes of Health Grants AI31268 and CA80312. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Chemical Immunology and Therapeutics Research Center, Department of Pathology and Laboratory Medicine, University of Texas, Houston Medical School, 6431 Fannin, Houston, TX 77030. Fax: 713-500-0574; E-mail: Sudhir.Paul{at}uth.tmc.edu.

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