Two major types of B cells, the antibody-producing cells of the immune
system, are classically distinguished in the spleen: marginal zone (MZ) and
follicular (FO). In addition, FO B cells are subdivided into FO I and FO II
cells, based on the amount of surface IgM. MZ B cells, which surround the
splenic follicles, rapidly produce IgM in response to blood-borne pathogens
without T cell help, while T cell-dependent production of high affinity,
isotype-switched antibodies is ascribed to FO I cells. The significance of FO
II cells and the mechanism underlying B cell fate choices are unclear. We
showed that FO II cells express more Sca1 than FO I cells and originate
from a distinct B cell development program, marked by high expression of
Sca1. MZ B cells can derive from the “canonical” Sca1lo pathways, as well
as from the Sca1hi program, although the Sca1hi program shows a stronger
MZ bias than the Sca1lo program, and extensive phenotypic plasticity exists
between MZ and FO II, but not between MZ and FO I cells. The Sca1hi
program is induced by hematopoietic stress and generates B cells with an
Igλ-enriched repertoire. In aged mice, the canonical B cell development
pathway is impaired, while the Sca1hi program is increased. Furthermore, we
showed that a population of unknown function, defined as Lin-c-kit+Sca1+
(LSK-), contains early lymphoid precursors, with primarily B cell potential
in vivo. Our data suggest that LSK- cells may represent a distinct precursor
for the Sca1hi program in the bone marrow.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:699 |
| Date | 23 May 2008 |
| Creators | Fossati, Valentina <1978> |
| Contributors | Bagnara, Gian Paolo |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/restrictedAccess |
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