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. Brüggemann
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