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) Data Supplement 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Zou, X. Articles by Brüggemann, M. Search for Related Content PubMed PubMed Citation Articles by Zou, X. Articles by Brüggemann, M. Pubmed/NCBI databases Gene GEO Profiles UniGene Substance via MeSH

Expression of a Dromedary Heavy Chain-Only Antibody and B Cell Development in the Mouse¹

Xiangang Zou^*, Jennifer A. Smith^*, Viet Khong Nguyen^2,, Liming Ren^3,*, Kattie Luyten^*, Serge Muyldermans and Marianne Brüggemann^4,*

^* Protein Technologies Laboratory, The Babraham Institute, Babraham, Cambridge, United Kingdom; and Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Brussels, Belgium

In mature B cells of mice and most mammals, cellular release of single H chain Abs without L chains is prevented by H chain association with Ig-specific chaperons in the endoplasmic reticulum. In precursor B cells, however, surface expression of µ-H chain in the absence of surrogate and conventional L chain has been identified. Despite this, Ag-specific single H chain Ig repertoires, using µ-, -, -, or -H chains found in conventional Abs, are not produced. Moreover, removal of H chain or, separately, L chain (/) locus core sequences by gene targeting has prevented B cell development. In contrast, H chain-only Abs are produced abundantly in Camelidae as H2 IgG without the C_H1 domain. To test whether H chain Abs can be produced in mice, and to investigate how their expression affects B cell development, we introduced a rearranged dromedary 2a H chain into the mouse germline. The dromedary transgene was expressed as a naturally occurring Ag-specific disulphide-linked homodimer, which showed that B cell development can be instigated by expression of single H chains without L chains. Lymphocyte development and B cell proliferation was accomplished despite the absence of L chain from the BCR complex. Endogenous Ig could not be detected, although V(D)J recombination and IgH/L transcription was unaltered. Furthermore, crossing the dromedary H chain mice with mice devoid of all C genes demonstrated without a doubt that a H chain-only Ab can facilitate B cell development independent of endogenous Ig expression, such as µ- or -H chain, at early developmental stages.

This article has been cited by other articles:

				I. Achour, P. Cavelier, M. Tichit, C. Bouchier, P. Lafaye, and F. Rougeon Tetrameric and Homodimeric Camelid IgGs Originate from the Same IgH Locus J. Immunol., August 1, 2008; 181(3): 2001 - 2009. [Abstract] [Full Text] [PDF]

				X. Zou, M. J. Osborn, D. J. Bolland, J. A. Smith, D. Corcos, M. Hamon, D. Oxley, A. Hutchings, G. Morgan, F. Santos, et al. Heavy chain only antibodies are spontaneously produced in light chain deficient mice J. Exp. Med., December 24, 2007; 204(13): 3271 - 3283. [Abstract] [Full Text] [PDF]

				P. Geraldes, M. Rebrovich, K. Herrmann, J. Wong, H.-M. Jack, M. Wabl, and M. Cascalho Ig Heavy Chain Promotes Mature B Cell Survival in the Absence of Light Chain J. Immunol., August 1, 2007; 179(3): 1659 - 1668. [Abstract] [Full Text] [PDF]

				R. Janssens, S. Dekker, R. W. Hendriks, G. Panayotou, A. v. Remoortere, J. K.-a San, F. Grosveld, and D. Drabek Generation of heavy-chain-only antibodies in mice PNAS, October 10, 2006; 103(41): 15130 - 15135. [Abstract] [Full Text] [PDF]