Characterized by a greater, faster and more specific antibody response alter repeated immunization, immunological memory is still poorly understood and yet widely manipulated for the prevention of disease. The overall goal of the proposed research is to characterize the means by which a B-cell memory response is generated from naive B-cells and to define the requirements for the maintenance of such responses. To elucidate the elements of B-cell memory, a novel experimental system in mice was generated. These mice (monoclonal B-T mice) have a knock-in heavy-chain gene, a transgenic lambda light chain and a transgenic T helper T-cell receptor. Because they are engineered in a V(D)J recombinase-negative background, the primary antibody repertoire is monoclonal and can be diversified in response to immunization. In this way, by immunization with a hapten-carrier conjugate, a memory response and memory B-cells are generated. In one variant of the mouse models, the immunoglobulin expression by the B-cells will be regulated by the tet repressor system (Inducible immunoglobulin mice). In these mice, generation of B-cells memory will be studied under various conditions of surface Ig expression by the B-cells. One goal of these studies is to determine whether memory B-cells in addition to plasma cells can be identified after a primary response and whether memory B-cells have an activated or resting phenotype. Another goal is to determine whether expression surface Ig on B-cells will affect cell differentiation to effector-plasma cell vs. memory cell upon engagement by antigen. These goals will be achieved by analysis of the antigen specific Ig titer and by analysis of somatic hypermutation of the heavy-chain V exons following immunization with the cognate antigen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048602-04
Application #
6733556
Study Section
Immunobiology Study Section (IMB)
Program Officer
Chiodetti, Lynda
Project Start
2001-04-23
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
4
Fiscal Year
2004
Total Cost
$282,200
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Cascalho, Marilia I; Chen, Brian J; Kain, Mandy et al. (2013) The paradoxical functions of B cells and antibodies in transplantation. J Immunol 190:875-9
AbuAttieh, Mouhammed; Bender, Diane; Liu, Esther et al. (2012) Affinity maturation of antibodies requires integrity of the adult thymus. Eur J Immunol 42:500-10
Platt, Jeffrey L; Tsuji, Shoichiro; Cascalho, Marilia (2011) Novel functions of B cells in transplantation. Curr Opin Organ Transplant 16:61-8
Balin, Samuel J; Platt, Jeffrey L; Cascalho, Marilia (2008) New insights into the functions of B cells. Pediatr Transplant 12:510-5
Martin, Denise A; Lu, Liwei; Cascalho, Marilia et al. (2007) Maintenance of surrogate light chain expression induces developmental delay in early B cell compartment. J Immunol 179:4996-5005
Cascalho, Marilia; Platt, Jeffrey L (2006) B cells and B cell products-helping to restore cellular immunity? Transfus Med Hemother 33:45-49