Advisory Committee Chair
Louis B Justement
Advisory Committee Members
Daniel C Bullard
Peter D Burrows
David D Chaplin
John F Kearney
Document Type
Dissertation
Date of Award
2011
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Germinal Centers (GC) are organized foci in secondary lymphoid organs of birds and mammals and are the principle sites of memory B cell generation and plasma cell formation. GC concentrate antigen within follicles to facilitate recognition by responding B cells to promote somatic hypermutation and affinity maturation. Follicular dendritic cells (FDC) reside within the light zones of GC and serve to facilitate B cell interactions with antigen, as well as B cell selection, proliferation, and survival. The work contained within this dissertation addresses the collaborative interactions between B cells and FDC. FDC within an active, GC-containing follicle express an array of molecules that play a role in promoting high affinity antibody production. The processes involved in the development of FDC in GC-containing follicles from FDC in resting follicles are poorly understood. Additionally, the proposed signals that drive FDC activation are indispensable for primary FDC development, therefore blocking these signals results in the loss of the FDC population. CD19-deficient mice have normal numbers of FDC containing follicles, but lack the ability to activate FDC, providing a model by which to study FDC activation. Using VCAM-1 and FcyRII/III as FDC activation markers, we show that antigen binding to FDC alone is not sufficient to drive FDC activation, but rather it is due to CD19-dependent B cell activation. The adoptive transfer of WT B cells into CD19-deficient mice rescues FDC activation. CD19-deficient mice receiving donor B cells lacking membrane-LT (mLT), however, fails to upregulate VCAM-1 expression and, as well as FcyRII/III on FDC, despite the presence of GC. FDC activation was partially rescued when CD19-deficient B cells expressing transgenic mLT were cotransferred with CD19+ mLT- B cells into CD19-/- recipients, suggesting that mLT on B cells is required for the activation of FDC and that this is CD19-dependent. This suboptimal FDC activation may be the result of interrupted mLT signaling due to the limited survival of the mLT transgenic B cells. Collectively, these data suggest that activated B cells are responsible for the initiation of FDC activation resulting in a microenvironment supportive for the development and maintenance of the germinal center reaction.
Recommended Citation
Myers, Riley Croom, "The Role of CD19 in Follicular Dendritic Cell Activation" (2011). All ETDs from UAB. 2549.
https://digitalcommons.library.uab.edu/etd-collection/2549
