During a T-dependent immune response, activated B cells enter structures called germinal centers (GC) in the follicles of secondary lymphoid organs. GC B cells proliferate and undergo diversification of their Ig through somatic hypermutation and class-switch recombination. These Ig diversifications require the activity of the enzyme activation-induced deaminase (AID). Clonal selection within GCs selects GC B cells with the highest affinities for antigen to mature into plasma cells and memory B cells. GCs are underpinned by stromal cells called follicular dendritic cells (FDC). FDC functions include secretion of B cell chemokines and the retention of Ag complexes that allow GC B cells to test the affinity of their Ig. FDCs require constitutive signaling through lymphotoxin beta receptor (LTβR) from lymphotoxin alpha-beta (LTαβ) on the surface of B cells to maintain their functions. In these studies, I investigated the properties of GCs using two primary experimental models. First, I employed genetic and pharmacological ablation of LTβR signaling to investigate the expression of AID and the function of GCs in the absence of FDCs. I determined that FDCs are not required for GC formation or the expression of AID in lymph nodes, but that FDCs are crucial for affinity maturation. Second, I examined the competition between AID-/- and WT B cells in the GCs of mixed BM chimeras to investigate the role of affinity maturation during clonal selection. I found that AID increases GC B cell apoptosis, likely by inducing DNA damage, and that this is important in regulating GC size. I also found that AID-/- B cells accumulate at the centrocyte stage of the GC reaction and that this is due to a partial block in plasma cell maturation.

Zugl.: Rostock, Univ., Diss., 2005

Zugl.: Maastricht, Univ., Master-Thesis, 2004

Zugl.: Hamburg, Univ., Diss., 2008

Thesis (Ph. D.)--University of Rhode Island, 2004. / Typescript. Includes bibliographical references (leaves v. 3, 557-568).

Konstanz, Univ., Diplomarb., 2004.

Thesis (Ph. D.)--University of California, Los Angeles, 1995. / Thesis prepared for Dept. of Music. Includes vita and abstract. Includes bibliographical references ((leaves 192-205)).

Univ. Konstanz, Habil.-Schr., 2004.

Thesis (M.A.)--University of Wisconsin--Madison, 1964. / eContent provider-neutral record in process. Description based on print version record.

Thesis (M.S.)--University of Wisconsin. School of Nursing, 1976. / eContent provider-neutral record in process. Description based on print version record.