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 Ig H/L transcription was unaltered.
Developmental progression is blocked at the pre-B-I cell stage when H chain expression is prevented, although H and/or L chain transcripts may be found (2, 3).
Likewise, silencing of both κ- and chain loci blocks B cell development, but at the somewhat later pre-B-II stage, which allows normal development up to pre-BCR expression (4).
Furthermore, crossing the dromedary H chain mice with mice devoid of all In the conventional mouse and human immune system, B cell development is initiated by VDJ recombination and surface Ig M expression (Ref.1 , and refs. At the pre-B cell stage, the associated surrogate L chain is replaced with a κ- or λ-L chain, and this initiates the process of Ab maturation, which is accompanied by cellular migration and class switching.
At this stage, mature B cells undergo further selection and affinity maturation and can differentiate into Ab-secreting plasma cells or memory cells bearing other isotypes (Ig G, Ig A, or Ig E).
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-, γ-, ε-, or α-H chains found in conventional Abs, are not produced. 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 γ2a 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.