Heavy chain-only antibodies are spontaneously produced in light chain-deficient mice

In healthy mammals, maturation of B cells expressing heavy (H) chain immunoglobulin (Ig) without light (L) chain is prevented by chaperone association of the H chain in the endoplasmic reticulum. Camelids are an exception, expressing homodimeric IgGs, an antibody type that to date has not been found...

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Published in:The Journal of experimental medicine 2007-12, Vol.204 (13), p.3271-3283
Main Authors: Zou, Xiangang, Osborn, Michael J, Bolland, Daniel J, Smith, Jennifer A, Corcos, Daniel, Hamon, Maureen, Oxley, David, Hutchings, Amanda, Morgan, Geoff, Santos, Fatima, Kilshaw, Peter J, Taussig, Michael J, Corcoran, Anne E, Brüggemann, Marianne
Format: Article
Language:English
Subjects:
Alleles
Animals
Antibodies - chemistry
Blotting, Western
Cell Line
DNA - metabolism
Flow Cytometry
Genes, Immunoglobulin
Immune System
Immunoglobulin Heavy Chains - metabolism
Immunoglobulin Light Chains - metabolism
In Situ Hybridization, Fluorescence
Mice
Recombination, Genetic
Reverse Transcriptase Polymerase Chain Reaction
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Summary:In healthy mammals, maturation of B cells expressing heavy (H) chain immunoglobulin (Ig) without light (L) chain is prevented by chaperone association of the H chain in the endoplasmic reticulum. Camelids are an exception, expressing homodimeric IgGs, an antibody type that to date has not been found in mice or humans. In camelids, immunization with viral epitopes generates high affinity H chain-only antibodies, which, because of their smaller size, recognize clefts and protrusions not readily distinguished by typical antibodies. Developmental processes leading to H chain antibody expression are unknown. We show that L(-/-) (kappa(-/-)lambda(-/-)-deficient) mice, in which conventional B cell development is blocked at the immature B cell stage, produce diverse H chain-only antibodies in serum. The generation of H chain-only IgG is caused by the loss of constant (C) gamma exon 1, which is accomplished by genomic alterations in C(H)1-circumventing chaperone association. These mutations can be attributed to errors in class switch recombination, which facilitate the generation of H chain-only Ig-secreting plasma cells. Surprisingly, transcripts with a similar deletion can be found in normal mice. Thus, naturally occurring H chain transcripts without C(H)1 (V(H)DJ(H)-hinge-C(H)2-C(H)3) are selected for and lead to the formation of fully functional and diverse H chain-only antibodies in L(-/-) animals.
ISSN:0022-1007
1540-9538
1892-1007
DOI:10.1084/jem.20071155