Abstract

The proposed experiments are designed to further our understanding of the formation and utilization of antibody structural diversity by the murine immune system towards creation of specificity for antigen and acquisition of a state of immunity. These experiments will directly address the following questions: 1) What fraction of antibody diversity is formed during the development of an immune response and how is such diversity created? 2) Does the immune system utilize available antibody diversity in fundamentally different ways depending on dose and type of antigen? 3) Do T lymphocytes? and 4) Do all members of the B cell population have an equal potential for creation of antibody diversity?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI023739-01
Application #
3136087
Study Section
Immunobiology Study Section (IMB)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
Princeton University
Department
Type
Schools of Arts and Sciences
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544

  Publications

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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