Title

Altered B Cell Development In Aging

Date of Award

2004

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Microbiology and Immunology

First Committee Member

Richard L. Riley, Committee Chair

Abstract

We have described a distinct bone marrow immature B cell population in non-transgenic, adult BALB/c mice characterized by expression of CD43/S7 and large cell size. In young (2--4 month) BALB/c mice, this sub-population constitutes a relatively minor component of total bone marrow immature B cells. However, with old age (>20 months), the frequency of CD43/S7+ immature B cells in the bone marrow of BALB/c mice increases. A requirement for an intact Btk-associated BCR signaling cascade for optimal development of the CD43/S7+ phenotype, as well as expression of surface antigens associated with BCR-mediated activation of B cells (e.g. CD5, CD11b, PD-1), suggest CD43/S7+ immature B cells in both young and aged BALB/c mice are likely partially activated, presumably in a BCR-associated manner. In addition, the CD43/S7+ immature B cell sub-population showed an increased frequency of kappa and lambda light chain co-expression, suggesting this population may be enriched with cells undergoing tolerance mechanisms. Moreover, kappa and lambda light chain co-expression combined with results indicating a bias in VH repertoire (e.g. VHS107) may suggest recruitment into the CD43/S7+ sub-population is driven by BCR. Notably, selection into the CD43/S7+ immature B cell compartment appears to be preferentially maintained in instances of both naturally occurring and induced pre-B and immature B cell depletions. We propose that the apparent selective maintenance of CD43/S7+ immature B cells under conditions of normal aging or induced apoptosis, specific for pre-B and immature B cells, likely results from not only increased longevity and survival of CD43/S7+ immature B cells, but also alterations in pre-B cell development which favor production of immature B cells capable of partial activation within the bone marrow.

Keywords

Health Sciences, Immunology

Link to Full Text

http://access.library.miami.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3125390