Expression of a dromedary heavy chain-only antibody and B cell development in the mouse.
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.
Zou
Xiangang
X
Protein Technologies Laboratory, The Babraham Institute, Babraham, Cambridge, United Kingdom.
Smith
Jennifer A
JA
Nguyen
Viet Khong
VK
Ren
Liming
L
Luyten
Kattie
K
Muyldermans
Serge
S
Brüggemann
Marianne
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D002162:Camelus; D049109:Cell Proliferation; D019281:Dimerization; D025461:Feedback, Physiological; D015321:Gene Rearrangement; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000502:physiology*; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D014158:Transcription, Genetic
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins