Altered B Cell Development In Aging
Date of Award
Doctor of Philosophy (Ph.D.)
Microbiology and Immunology
First Committee Member
Richard L. Riley - Committee Chair
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.
Health Sciences, Immunology
Wilson, Emily Anne, "Altered B Cell Development In Aging" (2004). Dissertations from ProQuest. 2077.