Rose G. Mage, Ph.D.

Description of Research Program

The goals are to understand the development of the immune system with special emphasis on the cells (B lymphocytes) that develop to produce protective antibodies in the blood and at mucosal surfaces in response to vaccines and infections. Mucosal surfaces, such as those of the respiratory, digestive, and genito-urinary tracts are important sites of invasion of infectious organisms ranging from those causing sexually transmitted diseases to tuberculosis, influenza, and cholera. Characterized are genes that code for antibody molecules as well as a variety of genes that are needed to regulate development of the cells producing these molecules.

Molecular Immunogenetics Section scientists use tools of genetics and cell and molecular biology, and use the rabbit as an animal model. In the rabbit, the appendix is an important site of development of the cells destined to produce protective antibodies. In the young rabbit, there is rapid growth and expansion of these B lymphocytes, but there is also considerable cell death. Positive selection for growth and survival of developing cells occurs via signals directed through copies of the antibody molecules that appear on the surfaces of the developing cells. Those cells that are growing and expanding in numbers have higher levels of a protein (Bcl-2) than those that are not. The presence of this protein inside the cell has been shown to confer resistance to some types of programmed cell death.

It was previously shown that a mutant rabbit (ali) has a deletion of an important gene necessary for production of antibody molecules. The development of B lymphocytes is affected by the absence of the gene that is normally used to code for the majority of rabbit antibodies. In mutant rabbits, the development of the appendix is thus retarded; however, in time, a compensatory mechanism allows development and expansion of B lymphocytes. These cells have surface antibody molecules that mimic the structures coded for by the missing gene. It is believed these structures were generated by a mechanism like that found in lower organisms (yeast and fungi) called gene conversion. This mechanism allows one gene to be converted in part to resemble another. The rabbit appears to use such a mechanism to make a variety of different antibody molecule structures that can recognize a variety of different foreign antigens (molecules on invading organisms). Studies of human embryonic development show that the distal midgut and ileocecal portion of the digestive system, including the appendix, are developmentally homologous with the bursa of Fabricius. The researchers are conducting a new evaluation of the role of human appendix and GALT in development of mucosal immunity and the human immune repertoire.

A working model of B-cell repertoire development in the rabbit.

Memberships

• American Society for Microbiology
• Sigma Xi
• American Association of Immunologists
• Canadian Society for Immunology
• American Association for the Advancement of Science
• New York Academy of Science

Advisory/Review Boards

• NIAID Research Contract Approval Group
• ASM Immunology Division
• AAI Representative to American Type Culture Collection
• Executive Committee of the ATCC Board of Directors
• Foundation for Advanced Education in the Sciences (NIH)

Editorial Boards

• Federation Proceedings
• Immunochemistry
• Allergy and Immunology Study Section
• The Journal of Immunology
• The Journal of Immunological Methods
• Immunogenetics

Research Group Members

Cornelius B. Alexander, Glendowlyn O. Young-Cooper, Devinder Sehgal, Joseph Dasso, Harold Obiakor.

Selected Publications

(View list in PubMed.)

Pospisil R, Alexander CB, Obiakor H, Sinha RK, Mage RG. CD5+ B cells are preferentially expanded in rabbit appendix: the role of CD5 in B cell development and selection. Dev Comp Immunol. 2006;30(8):711-22.

Rai G, Ray S, Shaw RE, Degrange PF, Mage RG, Newman BA.
Models of systemic lupus erythematosus: development of autoimmunity following peptide immunizations of noninbred pedigreed rabbits. J Immunol. 2006 Jan 1;176(1):660-7. 

Yang G, Obiakor H, Sinha RK, Newman BA, Hood BL, Conrads TP, Veenstra TD, Mage RG. Activation-induced deaminase cloning, localization, and protein extraction from young VH-mutant rabbit appendix. Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17083-8.

Sinha RK, Alexander C, Mage RG. Regulated expression of peripheral node addressin-positive high endothelial venules controls seeding of B lymphocytes into developing neonatal rabbit appendix. Vet Immunol Immunopathol. 2006 Mar 15;110(1-2):97-108. 

Mage RG, Lanning D, Knight KL. B cell and antibody repertoire development in rabbits: the requirement of gut-associated lymphoid tissues. Dev Comp Immunol. 2006;30(1-2):137-53. 

Pospisil R, Obiakor H, Newman BA, Alexander C, Mage RG.
Stable expression of the extracellular domains of rabbit recombinant CD5: development and characterization of polyclonal and monoclonal antibodies. Vet Immunol Immunopathol. 2005 Feb 10;103(3-4):257-67.

Special Interest Groups
Immunology, Structural Biology, Genetics.

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