We use classical immunogenetic techniques as well as techniques of molecular biology to study the genetics of rabbit immunoglobulins (Igs) and T cell receptors and the regulated expression of the genes that encode these molecules. A rabbit cDNA copy of splenic mRNA is spliced to C mu from a site 635 bp 3' of the conserved octanucleotide of the heavy chain enhancer. A splice site is present at a similar position in the intron sequences of mouse and man. There is evidence that such spliced steril transcripts occur in developing B cells of mice and in some human cell lines. The evolutionary conservation of the spliced mRNA in these three species suggest that it may play a functional role during B cell ontogeny. We are characterizing T cell receptor C beta genes from rabbits which have three copies of the C beta constant region. We previously demonstrated that there are allotypes of rabbit C beta1. We have now sequenced about 4 kb of cloned 6 kb fragment from an animal of type b and demonstrated that this fragment contains a rabbit C beta2 gene. Comparisons with the cDNA sequence from an animal of C beta type a show replacement changes in the first and third exons thus demonstrating that there are also allotypic forms of C beta2. Decreased galactosylation of IgG that is observed in a sera of rheumatoid patients is also observed in the IgG prepared from sera of rabbits post-immunization with Streptococcal vaccines. Therefore the difference in IgG galactosylation seen in patients may also be induced rather than reflect an inherent genetic difference in individuals with rheumatoid disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000036-24
Application #
3818092
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Pospisil, Richard; Alexander, Cornelius B; Obiakor, Harold et al. (2006) CD5+ B cells are preferentially expanded in rabbit appendix: the role of CD5 in B cell development and selection. Dev Comp Immunol 30:711-22
Sinha, Rajesh K; Alexander, Cornelius; Mage, Rose G (2006) Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix. Vet Immunol Immunopathol 110:97-108
Sinha, Rajesh K; Yang, Guibin; Alexander, Cornelius et al. (2006) De novo expression of MECA-79 glycoprotein-determinant on developing B lymphocytes in gut-associated lymphoid tissues. Immunology 119:461-9
Yang, Guibin; Obiakor, Harold; Sinha, Rajesh K et al. (2005) Activation-induced deaminase cloning, localization, and protein extraction from young VH-mutant rabbit appendix. Proc Natl Acad Sci U S A 102:17083-8
Pospisil, Richard; Obiakor, Harold; Newman, Barbara A et al. (2005) Stable expression of the extracellular domains of rabbit recombinant CD5: development and characterization of polyclonal and monoclonal antibodies. Vet Immunol Immunopathol 103:257-67
Sinha, Rajesh K; Mage, Rose G (2004) Developing neonatal rabbit appendix, a primary lymphoid organ, is seeded by immature blood-borne B cells: evidence for roles for CD62L/PNAd, CCR7/CCL21, alpha4beta1 and LFA-1. Dev Comp Immunol 28:829-41
Taylor, Marcia L; Sehgal, Devinder; Raffeld, Mark et al. (2004) Demonstration that mast cells, T cells, and B cells bearing the activating kit mutation D816V occur in clusters within the marrow of patients with mastocytosis. J Mol Diagn 6:335-42
Sehgal, Devinder; Obiakor, Harold; Mage, Rose G (2002) Distinct clonal Ig diversification patterns in young appendix compared to antigen-specific splenic clones. J Immunol 168:5424-33
Obiakor, Harold; Sehgal, Devinder; Dasso, Joseph F et al. (2002) A comparison of hydraulic and laser capture microdissection methods for collection of single B cells, PCR, and sequencing of antibody VDJ. Anal Biochem 306:55-62
Sehgal, D; Schiaffella, E; Anderson, A O et al. (2000) Generation of heterogeneous rabbit anti-DNP antibodies by gene conversion and hypermutation of rearranged VL and VH genes during clonal expansion of B cells in splenic germinal centers. Eur J Immunol 30:3634-44

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