The unique immunobiology of transitional B cells : implications for modulation of T cell responses and B cell negative selection / James B. Chung.

Format:

Book

Manuscript

Microformat

Thesis/Dissertation

Author/Creator:

Chung, James B.

Contributor:

Monroe, John G., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Allergy and Immunology.

Academic Dissertations as Topic.

Medical Subjects:

Allergy and Immunology.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Immunology.

Immunology--Penn dissertations.

Physical Description:

xi, 156 pages : color illustrations ; 29 cm

Production:

2002.

Summary:

Transitional B cells undergo apoptosis in vitro with BCR ligation, and thus represent a major target of negative selection in vivo. T cell help signals can rescue antigen induced apoptosis in transitional B cells suggesting a role for T cell help in modulating B cell negative selection, but the nature of the interaction between transitional B cells and naive T cells is not well understood. Transitional B cells were found to consist of developmentally contiguous subsets based on their surface expression of CD23. CD23+ transitional B cells proliferated more vigorously, and were rescued from BCR-induced apoptosis to a greater degree, by T cell help. Unlike their CD23- counterparts, CD23+ transitional B cells gained access to B cell follicles enriched in antigen and activated T cells. Transitional B cells (CD23 - and CD23+) were found to be as capable of processing and presenting antigen onto the cell surface as mature B cells, but CD4 T cells were found to proliferate less and to produce dramatically decreased amounts of IL-2 in co-culture with them compared with mature B cells in a co-stimulation dependent manner. Cognate interactions with CD4 T cells rescued transitional B cells from undergoing anti-BCR induced apoptosis, and this protection was antigen specific, dose dependent, and augmented by anti-CD28. Lastly, we found that mature B cells co-polarize the BCR with glycosphingolipid enriched domains (GEDs), known as lipid rafts, following BCR aggregation whereas transitional B cells do not. Although anti-BCR treatment leads to receptor aggregation by transitional B cells, the aggregated complexes do not co-localize with GEDs suggesting a structural basis for the developmentally regulated differences observed in antigen receptor mediated signal transduction. These results demonstrate the complexities of transitional B cell biology as it relates to susceptibility to negative selection, their interaction with CD4 T cells, and to the maturation of signaling mechanisms downstream of the antigen receptor. These remarkable cells have the potential to affect the response and selection of both T and B cell compartments with implications for tolerance and autoimmunity.

Notes:

Adviser: John G. Monroe.

Thesis (Ph.D. in Immunology) -- University of Pennsylvania, 2002.

Includes bibliographical references.

Local Notes:

University Microfilms order no.: 3072985.

OCLC:

244971626