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Studies of adaptive immune responses: factors mediating the biology of adaptive T regulatory cells, plasma cells, and memory B cells.

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Call No.	QR186 .B46 2008
Author	Benson, Micah James.
Title	Studies of adaptive immune responses: factors mediating the biology of adaptive T regulatory cells, plasma cells, and memory B cells.
Date	2008
Abstract	Adaptive immunity licenses higher organisms to generate potent immune responses against foreign antigens. Two hallmarks of adaptive immunity are A) the ability of T and B cells to distinguish self from non-self and B) the ability to mount a qualitatively and quantitatively superior immune response upon secondary exposure to antigens. Due to the essential role of adaptive immunity in human disease, the soluble factors mediating the basic biology of cells within the adaptive immune system are of great importance. The gut is an anatomical situation where immune responses are chronically suppressed and the mechanism of how this occurs remains unknown. The studies presented demonstrate that all- trans retinoic acid, a factor found in great abundance in the gut, greatly enhances the induction of a suppressive population of cells called adaptive T regulatory cells. All- trans retinoic acid is thus a newly identified differentiation factor for T regulatory cells. These data implicates all- trans retinoic acid as an essential mediator of gut tolerance in vivo. Memory B cells and long-lived bone marrow plasma cells are the cellular constituents of humoral memory. The in vivo factors supporting memory B cell and plasma cell survival remain poorly characterized. We find that memory B cell survival and function is independent of the factors B-cell activating factor of the TNF family (BAFF) and a-proliferation inducing ligand (APRIL). These studies also find that BAFF and APRIL are redundant in their ability to support the survival of long-lived plasma cells. These data define the BAFF and APRIL-dependent and -independent components of long-lived humoral immunity, and find that memory B cells and long-lived plasma cells occupy independent survival niches. Despite their in vivo longevity, memory B cells and long-lived plasma cells require replenishment. We find that memory B cells are capable of differentiating into plasma cells in response to antigen-independent activation, with naïve B cells unable to perform this function. These data implicate antigen-independent activation of memory B cells as a possible mechanism behind memory B cell renewal and long-lived plasma cell replenishment. Together, the soluble factors that mediate adaptive immunity are studied in this work.
Description	xi, 227 leaves : ill. (some col.) 28 cm.
Format	application/pdf
Advisor	Noelle, Randolph J. Sentman, Charles, Turk, Mary Jo, Geha, Raif School:
Subject	Immune response -- Regulation. Tretinoin. T cells. B cells. Plasma cells. Immunity.
College	Dartmouth Medical School -- Department of Microbiology and Immunology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.214

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	Studies of Adaptive Immune Responses: Factors Mediating the Biology of Adaptive T Regulatory Cells, Plasma Cells, and Memory B Cells A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Microbiology and Immunology By Micah James Benson DARTMOUTH COLLEGE Hanover, New Hampshire May, 2008 Examining Committee: (chair) Dr. Charles Sentman Dr. Randolph J. Noelle Dr. Mary Jo Turk Dr. Raif Geha Dr. Charles K. Barlowe Dean of Graduate Studies

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