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 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.
Zou
Xiangang
X
The Babraham Institute, Babraham, Cambridge CB22 3AT, England, UK.
Osborn
Michael J
MJ
Bolland
Daniel J
DJ
Smith
Jennifer A
JA
Corcos
Daniel
D
Hamon
Maureen
M
Oxley
David
D
Hutchings
Amanda
A
Morgan
Geoff
G
Santos
Fatima
F
Kilshaw
Peter J
PJ
Taussig
Michael J
MJ
Corcoran
Anne E
AE
Brüggemann
Marianne
M
D000483:Alleles; D000818:Animals; D000906:Antibodies / Q000737:chemistry; D015153:Blotting, Western; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D005434:Flow Cytometry; D005803:Genes, Immunoglobulin; D007107:Immune System; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism*; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D004247:DNA