HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Qian, Y. Articles by Clarke, S. H. Search for Related Content PubMed PubMed Citation Articles by Qian, Y. Articles by Clarke, S. H.

Dissecting the Anti-Desmoglein Autoreactive B Cell Repertoire in Pemphigus Vulgaris Patients¹

Ye Qian^*, Luis A. Diaz^2,*, Jian Ye and Stephen H. Clarke

^* Department of Dermatology and Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599; and National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894

Pemphigus vulgaris (PV) encompasses two clinical phenotypes, one producing mucosal blisters and the other mucosal and skin lesions (mcPV). The mucosal blister-producing PV variant is characterized by autoantibodies against desmoglein (Dsg)3, whereas mucosal and skin lesion-producing PV is characterized by autoantibodies to Dsg3 and Dsg1. The present study was aimed at disclosing the diversity and clonality of the anti-Dsg3 response, as well as whether anti-Dsg3 B cells are Ag selected. Human-mouse heterohybridomas were generated by fusion of EBV-transformed or freshly isolated PBLs from six PV patients with mouse myeloma cells. A total of 73 anti-Dsg hybridomas (47 IgM and 26 IgG) were isolated. Over 90% are specific for both Dsg1 and Dsg3 indicating extensive cross-reactivity between these responses. V_H gene segment use by IgM hybridomas is diverse, but is restricted among IgG hybridomas, where the majority uses one of two V_H genes. V_L gene segment use was diverse even among IgG hybridomas suggesting that the V_L is less critical to defining desmoglein specificity. Additionally, the IgG hybridomas were extensively mutated and the distribution and nature of the mutations suggested that they had been Ag selected. We conclude that the potentially pathogenic IgG anti-Dsg response is restricted in V_H use, is somatically mutated, and is Ag selected.

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.

¹ This work was supported in part by U.S. Public Health Service Grants R01-AR30281, R01-AR32599, and T32 AR07369 (to L.A.D.), and R01-AI43587 (to S.H.C.).

² Address correspondence and reprint requests to Dr. Luis A. Diaz, Department of Dermatology, University of North Carolina, 3100 Thurston Building, Campus Box No. 7287, Chapel Hill, NC 27599. E-mail address: ldiaz{at}med.unc.edu

³ Abbreviations used in this paper: PV, pemphigus vulgaris; Dsg, desmoglein; mPV, PV producing mucosal blisters; mcPV, PV producing mucosal and skin lesions; PF, pemphigus foliaceus; PB, peripheral blood; RT, reverse transcriptase; EC, ectodomain; FS, fogo selvagem; FWR, framework region; R, replacement; S, silent.