Details

Autor(en) / Beteiligte

• Zou, Xiangang
• Smith, Jennifer A
• Nguyen, Viet Khong
• Ren, Liming
• Luyten, Kattie
• Muyldermans, Serge
• Bruggemann, Marianne

Titel

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

Ist Teil von

• The Journal of immunology (1950), 2005-09, Vol.175 (6), p.3769-3779

Ort / Verlag

United States: Am Assoc Immnol

Erscheinungsjahr

2005

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.