Expression of a dromedary heavy chain-only antibody and B cell development in the mouse.

TitleExpression of a dromedary heavy chain-only antibody and B cell development in the mouse.
Publication TypeJournal Article
Year of Publication2005
AuthorsZou, X., J. A. Smith, V. Khong Nguyen, L. Ren, K. Luyten, S. Muyldermans, and M. Br├╝ggemann
JournalJ Immunol
Volume175
Issue6
Pagination3769-79
Date Published2005 Sep 15
ISSN0022-1767
KeywordsAnimals, B-Lymphocytes, Camels, Cell Proliferation, Dimerization, Feedback, Physiological, Gene Rearrangement, Immunoglobulin Heavy Chains, Immunoglobulin Variable Region, Immunoglobulins, Mice, Mice, Transgenic, Transcription, Genetic
Abstract

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 mu-H chain in the absence of surrogate and conventional L chain has been identified. Despite this, Ag-specific single H chain Ig repertoires, using mu-, gamma-, epsilon-, or alpha-H chains found in conventional Abs, are not produced. Moreover, removal of H chain or, separately, L chain (kappa/lambda) 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(H)1 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 gamma2a 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 mu- or delta-H chain, at early developmental stages.

Alternate JournalJ. Immunol.
PubMed ID16148123