The Rabbit CH Repertoire
Current Designation |
Chain & Haplotype |
Gene |
Serological Alleles |
Sequence Allele |
Major Features and Other Information | |
| IgG | γ d11e15 |
IGHG |
d11, e15 |
d11 Met, e15 Ala |
d11, d12 alleles in hinge region, position 225 | |
| γ d12e14 |
d12, e14 |
d12 Thr, e14 Thr |
e14, e15 alleles in CH2 domain, position 309 | |||
| γ d12e15 |
d12, e15 |
d12 Thr, e15 Ala |
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| IgA | α |
IGHA1 |
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2 |
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3 |
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4 |
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5 |
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6 |
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7 |
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8 |
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9 |
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10 |
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11 |
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12 |
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13 |
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| IgM | μ |
IGHM |
Secreted form from rabbit of a2 (F-1) haplotype | |||
| IgE | ε |
IGHE |
Sequence contained within this large BAC clone | |||
| IgD | Not Found |
Lanning et al., 2003; Ros et al., 2004; both found no evidence for IgD in cloned germline sequences |
References
Ros F, Puels J, Reichenberger N, van Schooten W, Buelow R, Platzer J, 2004, Sequence analysis of 0.5 Mb of the rabbit germline immunoglobulin heavy chain locus. Gene 330:49-59.
Lanning DK, Zhai SK, Knight KL, 2003, Analysis of the 3' Cmu region of the rabbit Ig heavy chain locus. Gene 309:135-144.
Mage, RG, Lanning D, Knight KL, 2006, B cell and antibody repertoire development in rabbits: The requirement of gut-associated lymphoid tissues. Developmental and Comparative Immunology 30:137-153.
The Rabbit CL Repertoire
Current Designation |
Chain & Haplotype |
Gene |
Serological Alleles |
Sequence Allele |
Major Features and Other Information | |
| Cκ1b4 | κ |
IGKC1 |
Four alleles in domestic and laboratory rabbit were originally defined serologically. The alleles encode multiple amino acid sequence differences. Different Jκ gene segments are associated with each Cκ1. | |||
| Cκ1b5 | ||||||
| Cκ1 | ||||||
| Cκ1b9 | ||||||
| Cκ1bbas | Cκ1bbas is a mutant of Cκ1b9k (see text) | |||||
| Cκ2bas1 | IGKC2 |
bas1 |
Leu 204 |
(a cDNA sequence) bas1 is detected serologically in mutant Basilea and parental b9k rabbits | ||
| Cκ2bas2 | bas2 |
Pro 204 |
bas2 is found in most laboratory strains. A distinct set of Jκ genes is associated with the Cκ2 genes | |||
| Cλ5 | λ c21 |
IGLC |
Gene organization differs in different rabbit strains. The serologically detectable types c7 and c21 appear to be isotypic rather than truly allelic form. Four other cλ (1-4) appear to be pseudogenes. | |||
| Cλ 6 | λ c7 |
Rabbit VH Repertoire: Germline genes used in VDJ gene rearrangements
Description |
Gene |
Sequence Allele |
Major Features and Other Information |
|
| VH1a1 | IGHV1 |
VH1a1* |
VH1 gene segments are the most frequently rearranged | |
| VH1a2 | VH1a2 |
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| VH1a3 | VH1a3 |
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| VHy33** | IGHVY33 |
The VHx, y, z and a few other genes are termed “a-negative” (VHa-) because their protein products do not react with the antibodies to VHa allotypes. In normal rabbits, “a-negative” Igs occur in 10 to 30% of the total IgG or Ig-bearing B cells | ||
| VHx32** | ||||
| VHz** | ||||
| VH611f** | ||||
| VHu1** | ||||
| VHx32b** | ||||
| VHx32c** |
* Most allelic forms were originally defined serologically. The a-locus alleles found in domestic and laboratory rabbits correspond to the genes mapping most 3’ (closest to the DH and JH regions) [1]. VH1 is found rearranged and expressed in most rabbit B lymphocytes [2, 3]. The IgH locus is estimated to contain 100-200 VH gene segments. Although some other VH genes rearrange, most VH gene segments may function primarily as donors for “gene conversion” of the rearranged VH1 sequence [2, 4]. Their expression is elevated in mutant Alicia rabbits [5] and in allotype-suppressed rabbits [6, 7] (see section 4).
** Only germline VH that are known to be expressed are tabulated. Except for y33, the germline genes have not been cloned; however, the finding of several recurring independently-derived cDNA sequences indicates that these sequences represent germline gene segments.
References
1. Knight KL, Becker RS, 1990, Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes: Implications for the generation of antibody diversity. Cell 60:963-970.
2. Becker RS, Knight KL, 1990, Somatic diversification of immunoglobulin heavy chain VDJ genes: Evidence for somatic gene conversion in rabbits. Cell 63:987-997.
3. Allegrucci M, Young-Cooper GO, Alexander CB, Newman BA, Mage RG, 1991, Preferential rearrangement in normal rabbits of the 3' VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation/conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences. Eur. J. Immunol. 21:411-417.
4. Weinstein PD, Anderson AO, Mage RG, 1994, Rabbit IgH sequences in appendix germinal centers: VH diversification by gene conversion-like and hypermutation mechanisms. Immunity 1:647-659.
5. Kelus AS, Weiss S, 1986, Mutation affecting the expression of immunoglobulin variable regions in the rabbit. Proc. Natl. Acad. Sci. USA 83:4883-4886.
6. Eskinazi DP, Knight KL, Dray S, 1979, Kinetics of escape from suppression of Ig heavy chain allotypes in multiheterozygous rabbits. Eur. J. Immunol. 9:276-283.
7. Short JA, Sethupathi P, Zhai SK, Knight KL, 1991, VDJ genes in VHa2 allotype-suppressed rabbits. Limited germline VH gene usage and accumulation of somatic mutations in D regions. J. Immunol. 147:4014-4018.
Biological Properties: