The proposed experiments are designed to provide insight into the molecular and cellular basis for humoral (antibody mediated) immunity. Such knowledge is of fundamental importance to the development of effective vaccination strategies, and for approaches to the generation of monoclonal antibodies for use in diagnostic and therapeutic applications. In particular, the experiments will examine how the antibodies expressed by an immune B cell population differ from those expressed by the """"""""naive"""""""" population, and whether these two populations differ in their potential for further differentiation. The immune response to the hapten p-azophenylarsonate (Ars) in strain A/j mice will be used as a model system. To directly examine the composition and differentiative capabilities of the Ars-induced immune B cell population in A/j mice, we will exploit the fact that this population can respond to the hapten p-azophenylsulfonate (Sulf), while the """"""""naive"""""""" B cell precursors to this immune population cannot. Using this approach, the following questions will be addressed: (1) Do changes in the structure and function of the antibodies expressed by the Ars-induced memory B cell population take place during secondary and higher order immune responses to Sulf? (2) How related in structure to Ars does a """"""""boosting"""""""" epitope have to be to elicit an immune response from the Ars-induced immune B cell population? (3) Does the Ars-immune B cell population produce a Sulf-boosted immune response in an irradiated mouse host (radiation chimera) that differs quantitatively of qualitatively from that observed in situ? and (4) Are the Ars-immune B cell population and the B cell population that generates the primary anti-Ars serum antibody response derived from different subpopulations of """"""""naive"""""""" B cell precursors?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023739-07
Application #
2062322
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1986-04-01
Project End
1996-07-31
Budget Start
1994-08-01
Budget End
1995-07-31
Support Year
7
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Heltemes-Harris, Lynn; Liu, Xiaohe; Manser, Tim (2005) An antibody VH gene that promotes marginal zone B cell development and heavy chain allelic inclusion. Int Immunol 17:1447-61
Alabyev, Boris; Manser, Tim (2002) Bcl-2 rescues the germinal center response but does not alter the V gene somatic hypermutation spectrum in MSH2-deficient mice. J Immunol 169:3819-24
Heltemes, Lynn M; Manser, Tim (2002) Level of B cell antigen receptor surface expression influences both positive and negative selection of B cells during primary development. J Immunol 169:1283-92
Lentz, V M; Manser, T (2001) Cutting edge: germinal centers can be induced in the absence of T cells. J Immunol 167:15-20
Vora, K A; Lentz, V M; Monsell, W et al. (2001) The T cell-dependent B cell immune response and germinal center reaction are intact in A-myb-deficient mice. J Immunol 166:3226-30
Tumas-Brundage, K M; Notidis, E; Heltemes, L et al. (2001) Predominance of a novel splenic B cell population in mice expressing a transgene that encodes multireactive antibodies: support for additional heterogeneity of the B cell compartment. Int Immunol 13:475-84
Lentz, V M; Manser, T (2000) Self-limiting systemic autoimmune disease during reconstitution of T cell-deficient mice with syngeneic T cells: support for a multifaceted role of T cells in the maintenance of peripheral B cell tolerance. Int Immunol 12:1483-97
Vora, K A; Tumas-Brundage, K M; Lentz, V M et al. (1999) Severe attenuation of the B cell immune response in Msh2-deficient mice. J Exp Med 189:471-82
Vora, K A; Tumas-Brundage, K; Manser, T (1999) Contrasting the in situ behavior of a memory B cell clone during primary and secondary immune responses. J Immunol 163:4315-27
Manser, T; Tumas-Brundage, K M; Casson, L P et al. (1998) The roles of antibody variable region hypermutation and selection in the development of the memory B-cell compartment. Immunol Rev 162:183-96

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