In mice, the germinal center (GC) supports post rearrangement diversification of Ig by V(D)J hypermutation and is necessary for the development of B memory cells. These processes require costimulus-dependent interactions between antigen-specific T and B lymphocytes and (factors from question mark) Follicullar dendritic cells (FDC). GCs also appear to serve as a peripheral site for the maintenance of self-tolerance by selective apoptosis. Indeed, in many ways this unique peripheral microenvironment recapitulates certain events of primary lymphogenesis; recently we have extended this recapitulation by the demonstration of abundant Rag-1, Rag-2, and TdT expression in GC centrocytes. Thus we propose to study the biological significance Rag and TdT expression in GCs, the role of mIg affinity in divine B cell activation proliferation, and selection, the structure of positively- and negatively selected anti-hapten antibodies, chromosomal fragmentation in GCs and the possibility of transforming translocations, and role of the CD21/CD19/TAPA-1 complex in selecting the memory B cell compartment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI024335-11
Application #
2003398
Study Section
Immunobiology Study Section (IMB)
Project Start
1989-07-01
Project End
2002-02-28
Budget Start
1997-03-01
Budget End
1998-02-28
Support Year
11
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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Holl, Eda K; O'Connor, Brian P; Holl, T Matt et al. (2011) Plexin-D1 is a novel regulator of germinal centers and humoral immune responses. J Immunol 186:5603-11
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Holl, T Matt; Haynes, Barton F; Kelsoe, Garnett (2010) Stromal cell independent B cell development in vitro: generation and recovery of autoreactive clones. J Immunol Methods 354:53-67
Chen, Huaiyong; Liao, Dongmei; Holl, T Matt et al. (2010) Genetic regulation of pristane-induced oil granuloma responses. Int J Exp Pathol 91:472-83

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